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Volume 29,Issue 5,2022 Table of Contents
2022, 29(5):383-390.
DOI: 10.3872/j.issn.1007-385X.2022.05.001
Abstract:
Human leukocyte antigen-E (HLA-E) is highly expressed in many kinds of cancer and associated with the prognosis of patients in a cancer-type-dependent manner. HLA-E plays an important anti-tumor immunomodulatory role mainly by binding to activating receptor (NKG2C) or inhibitory receptor (NKG2A) on NK cells or T cells. Based on this, targeting HLA-E/NKG2A to block the interaction of HLA-E with NKG2A or inhibit HLA-E expression may be one of the promising strategies for augmenting anti-tumor immune response. Based on the functional features of HLA-E, developing enhanced or universal engineered-T/NK cells adoptive cellular immunotherapies has the potential of enhancing the therapeutic effects of adoptive cellular immunotherapies, with good prospects in research and clinical application. How to effectively combine the strategy of targeting HLA-E/NKG2A with other immune therapies for more precise immunotherapy and better clinical therapeutic effects remains one of the challenges in the research and application of anti-tumor immuotherapies.
Human leukocyte antigen-E (HLA-E) is highly expressed in many kinds of cancer and associated with the prognosis of patients in a cancer-type-dependent manner. HLA-E plays an important anti-tumor immunomodulatory role mainly by binding to activating receptor (NKG2C) or inhibitory receptor (NKG2A) on NK cells or T cells. Based on this, targeting HLA-E/NKG2A to block the interaction of HLA-E with NKG2A or inhibit HLA-E expression may be one of the promising strategies for augmenting anti-tumor immune response. Based on the functional features of HLA-E, developing enhanced or universal engineered-T/NK cells adoptive cellular immunotherapies has the potential of enhancing the therapeutic effects of adoptive cellular immunotherapies, with good prospects in research and clinical application. How to effectively combine the strategy of targeting HLA-E/NKG2A with other immune therapies for more precise immunotherapy and better clinical therapeutic effects remains one of the challenges in the research and application of anti-tumor immuotherapies.
2022, 29(5):391-398.
DOI: 10.3872/j.issn.1007-385X.2022.05.002
Abstract:
With the rapid development of nano delivery systems (NDSs) and in-depth understanding of the mechanism of cell pyroptosis, a new tumor treatment strategy formed by an ingenious combination of the two has achieved certain effects in the experimental treatment of some tumors. The strategy of inducing pyroptosis of tumor cells based on NDSs can overcome the defects of using small molecule pyroptosis inducers alone, such as fast elimination in vivo, systemic serious adverse reactions and weak tumor-targeting ability. A variety of NDSs, such as liposomes, hydrogels, polymer micelles, metal-organic frameworks (MOFs) and cell membrane biomimetic nanocarriers, have been used to construct drugs that induce tumor cell pyroptosis. On this basis, a variety of strategies based on NDSs drug-induced tumor cell have been developed, including targeting tumor stem cells, interfering with ion homeostasis, promoting ROS production, inducing epigenetic changes and delivery of gasdermin (GSDM) family proteins, etc. However, to apply these strategies clinically we still faced insufficient understanding of the interaction mechanisms between nanomaterials and biological systems. In future researches, based on a comprehensive understanding of the interaction between nanomaterials and biological systems, if we can develop new and safe NDSs, combined with effective pyroptosis inducers to target and induce tumor cell pyroptosis, so as to overcome apoptosis escape and multidrug resistance, it is expected to bring good news to tumor patients.
With the rapid development of nano delivery systems (NDSs) and in-depth understanding of the mechanism of cell pyroptosis, a new tumor treatment strategy formed by an ingenious combination of the two has achieved certain effects in the experimental treatment of some tumors. The strategy of inducing pyroptosis of tumor cells based on NDSs can overcome the defects of using small molecule pyroptosis inducers alone, such as fast elimination in vivo, systemic serious adverse reactions and weak tumor-targeting ability. A variety of NDSs, such as liposomes, hydrogels, polymer micelles, metal-organic frameworks (MOFs) and cell membrane biomimetic nanocarriers, have been used to construct drugs that induce tumor cell pyroptosis. On this basis, a variety of strategies based on NDSs drug-induced tumor cell have been developed, including targeting tumor stem cells, interfering with ion homeostasis, promoting ROS production, inducing epigenetic changes and delivery of gasdermin (GSDM) family proteins, etc. However, to apply these strategies clinically we still faced insufficient understanding of the interaction mechanisms between nanomaterials and biological systems. In future researches, based on a comprehensive understanding of the interaction between nanomaterials and biological systems, if we can develop new and safe NDSs, combined with effective pyroptosis inducers to target and induce tumor cell pyroptosis, so as to overcome apoptosis escape and multidrug resistance, it is expected to bring good news to tumor patients.
2022, 29(5):399-409.
DOI: 10.3872/j.issn.1007-385X.2022.05.003
Abstract:
Objective: To analyze tumor-associated neutrophils (TANs) infiltration in EBV-positive nasopharyngeal carcinoma (NPC) tumor microenvironment (TME) and its correlation with the prognosis and clinicopathological features of patients with NPC, and to preliminarily investigate the role of TANs in activating CD8+ T cells in EBV-positive NPC. Methods: Tumor tissue specimens from 118 patients with EBV-positive NPC without metastases admitted to Sun Yat-sen University Cancer Center from 2008 to 2012 were collected. Immunohistochemistry was performed to analyze CD8+ T cells infiltration and TANs infiltration in NPC and their correlation with EBV infection, and to evaluate the infiltration of TANs in 118 human EBV-positive NPC tissue samples and analyze its correlation with the prognosis and clinicopathological features of NPC patients; flow cytometry was used to detect the expression of N2 marker (CD182 and CD206) of neutrophils stimulated by HK1-EBV-conditioned medium and the expression of CD69 and PD-1 of CD8+ T cells co-cultured with TANs. Results: There were more CD8+ T cells and neutrophils infiltrating in EBV-positive NPC where they were negatively correlated（P=0.0052）; densely infiltrated TANs in EBV-positive NPC tissues were positively correlated with poor prognosis of patients (P=0.025 in OS; P=0.027 in PFS); the infiltration of TANs was proved to be an independent risk factor for overall survival (P=0.035) in patients with NPC; compared with Control group, freshly isolated neutrophils cultured in HK1-EBV-conditioned medium showed an increased expression of N2 markers (P<0.001 in CD182; P<0.01 in CD206) which could suppress the expression of CD69 and promote the expression of PD-1 of CD8+ T cells. Conclusion: More TANs infiltrate in EBV-positive NPC where they polarize into N2 neutrophils, exerting an immunosuppressive effect by suppressing the activation of CD8+ T cells and having a positive correlation with the poor prognosis of NPC patients.
Objective: To analyze tumor-associated neutrophils (TANs) infiltration in EBV-positive nasopharyngeal carcinoma (NPC) tumor microenvironment (TME) and its correlation with the prognosis and clinicopathological features of patients with NPC, and to preliminarily investigate the role of TANs in activating CD8+ T cells in EBV-positive NPC. Methods: Tumor tissue specimens from 118 patients with EBV-positive NPC without metastases admitted to Sun Yat-sen University Cancer Center from 2008 to 2012 were collected. Immunohistochemistry was performed to analyze CD8+ T cells infiltration and TANs infiltration in NPC and their correlation with EBV infection, and to evaluate the infiltration of TANs in 118 human EBV-positive NPC tissue samples and analyze its correlation with the prognosis and clinicopathological features of NPC patients; flow cytometry was used to detect the expression of N2 marker (CD182 and CD206) of neutrophils stimulated by HK1-EBV-conditioned medium and the expression of CD69 and PD-1 of CD8+ T cells co-cultured with TANs. Results: There were more CD8+ T cells and neutrophils infiltrating in EBV-positive NPC where they were negatively correlated（P=0.0052）; densely infiltrated TANs in EBV-positive NPC tissues were positively correlated with poor prognosis of patients (P=0.025 in OS; P=0.027 in PFS); the infiltration of TANs was proved to be an independent risk factor for overall survival (P=0.035) in patients with NPC; compared with Control group, freshly isolated neutrophils cultured in HK1-EBV-conditioned medium showed an increased expression of N2 markers (P<0.001 in CD182; P<0.01 in CD206) which could suppress the expression of CD69 and promote the expression of PD-1 of CD8+ T cells. Conclusion: More TANs infiltrate in EBV-positive NPC where they polarize into N2 neutrophils, exerting an immunosuppressive effect by suppressing the activation of CD8+ T cells and having a positive correlation with the poor prognosis of NPC patients.
2022, 29(5):410-418.
DOI: 10.3872/j.issn.1007-385X.2022.05.004
Abstract:
Objective: To investigate the effect of polyadenosine diphosphate ribose polymerase 1 (PARP1) on the proliferation and 5-FU resistance of gastric cancer cells and its potential mechanism. Methods: The tumor tissues and corresponding paracancerous tissues of 72 patients with gastric cancer who were treated in Central Hospital of Enshi Tujia and Miao Autonomous Prefecture from May 2018 to December 2019 were collected. AGS cells were transfected with siFUT8 to knock down FUT8 gene expression. qPCR and immunohistochemistry were used to detect the expression of PARP1 in gastric cancer and adjacent tissues. CCK-8, flow cytometry, and colony formation assay were employed to detect the effects of AG14361 on the proliferation, apoptosis and colony formation of AGS cells. MTT assay was used to detect the effect of AG14361 on the 5-FU sensitivity of gastric cancer cells. The overall distribution of differential genes in AGS cells treated with AG14361 was analyzed by mRNA sequencing, and related signaling pathways were analyzed by KEGG enrichment. qPCR and WB were used to detect the expression of α-1,6-fucosyltransferase (FUT8) in AGS cells and the interference effect of FUT8. CCK-8, flow cytometry, and colony formation assay were employed to detect the effects of AG14361 on the proliferation, apoptosis, and colony formation of AGS cells disturbed by siFUT8. Results: Compared with paracancer tissues, PARP1 expression was significantly increased in gastric cancer tissues (P<0.001). AG14361 can significantly inhibit the proliferation and colony formation of AGS cells, thus promoting the apoptosis of AGS cells (all P<0.01). AG14361 treatment reduced the IC50 of 5-FU against gastric cancer cells, especially against AGS cells, with IC50 decreased by more than 60%. mRNA sequencing results showed that FUT8 was a key glycosyltransferase of AG14361 in inhibiting the proliferation of AGS cells (P<0.05). Compared with the siNC group, treatment of AG14361 with IC50 significantly reversed the promotion of AGS cells proliferation caused by inerference with FUT8, promoted apoptosis and BAX protein expression, decreased Bcl2 protein expression and inhibited the increase in AGS cell colony formation caused by interference with FUT8 (all P<0.01). Conclusion: PARP1 can promote malignant transformation of gastric cancer cells by regulating N-glycosyltransferase FUT8. AG14361 can enhance the chemotherapy sensitivity of 5-FU, and PARP1 may become a potential target for gastric cancer treatment.
Objective: To investigate the effect of polyadenosine diphosphate ribose polymerase 1 (PARP1) on the proliferation and 5-FU resistance of gastric cancer cells and its potential mechanism. Methods: The tumor tissues and corresponding paracancerous tissues of 72 patients with gastric cancer who were treated in Central Hospital of Enshi Tujia and Miao Autonomous Prefecture from May 2018 to December 2019 were collected. AGS cells were transfected with siFUT8 to knock down FUT8 gene expression. qPCR and immunohistochemistry were used to detect the expression of PARP1 in gastric cancer and adjacent tissues. CCK-8, flow cytometry, and colony formation assay were employed to detect the effects of AG14361 on the proliferation, apoptosis and colony formation of AGS cells. MTT assay was used to detect the effect of AG14361 on the 5-FU sensitivity of gastric cancer cells. The overall distribution of differential genes in AGS cells treated with AG14361 was analyzed by mRNA sequencing, and related signaling pathways were analyzed by KEGG enrichment. qPCR and WB were used to detect the expression of α-1,6-fucosyltransferase (FUT8) in AGS cells and the interference effect of FUT8. CCK-8, flow cytometry, and colony formation assay were employed to detect the effects of AG14361 on the proliferation, apoptosis, and colony formation of AGS cells disturbed by siFUT8. Results: Compared with paracancer tissues, PARP1 expression was significantly increased in gastric cancer tissues (P<0.001). AG14361 can significantly inhibit the proliferation and colony formation of AGS cells, thus promoting the apoptosis of AGS cells (all P<0.01). AG14361 treatment reduced the IC50 of 5-FU against gastric cancer cells, especially against AGS cells, with IC50 decreased by more than 60%. mRNA sequencing results showed that FUT8 was a key glycosyltransferase of AG14361 in inhibiting the proliferation of AGS cells (P<0.05). Compared with the siNC group, treatment of AG14361 with IC50 significantly reversed the promotion of AGS cells proliferation caused by inerference with FUT8, promoted apoptosis and BAX protein expression, decreased Bcl2 protein expression and inhibited the increase in AGS cell colony formation caused by interference with FUT8 (all P<0.01). Conclusion: PARP1 can promote malignant transformation of gastric cancer cells by regulating N-glycosyltransferase FUT8. AG14361 can enhance the chemotherapy sensitivity of 5-FU, and PARP1 may become a potential target for gastric cancer treatment.
2022, 29(5):419-425.
DOI: 10.3872/j.issn.1007-385X.2022.05.005
Abstract:
Objective: The co-culture model of LAG3+ Jurkat cells and tumor cells was constructed to investigate the anti-tumor effect and mechanism of a novel fully human anti-LAG3 monoclonal antibody in vitro. Methods: Jurkat cells were stimulated with PHA to simulate TIL, and the secretion of IL-2 was detected by ELISA to evaluate the degree of Jurkat cell activation. Meanwhile, FCM, Immunofluorescence and WB assays were employed to detect the expression of LAG3 in activated Jurkat cells and MHC classⅡ molecule（MHC-Ⅱ）, a LAG3 ligand, in HGC-27, MGC-803 and A549 tumor cells. The co-culture model of activated LAG3+ Jurkat cells and tumor cells was constructed, and CCK-8 assays were employed to detect the killing efficiency of LAG3+ Jurkat cells against tumor cells at different effector-target ratios and the effect of the anti-LAG3 antibody . The secretion levels of cytokines IL-2, IL-10 and TNF-α in supernatant of co-culture system were detected by ELISA. Results: After 48 h treatment, 2 μg/mL PHA exhibited no obvious cytotoxicity to Jurkat cells (P>0.05), but could significantly induce IL-2 secretion (P<0.01) and LAG3 expression (P<0.01), indicating activated LAG3+ Jurkat cells were acquired. MGC-803 and A549 cells significantly expressed MHC-Ⅱ (P<0.01), but HGC-27 cells did not express MHC-Ⅱ (P>0.05). The co-culture model of LAG3+ Jurkat cells and tumor cells was constructed at a effector-target ratio of 10∶1. The anti-LAG3 antibody could effectively enhance the killing efficiency of Jurkat cells against MHC-Ⅱ+ tumor cells (P<0.05). Further analysis revealed that the secretion levels of cytokines IL-2, IL-10 and TNF-α were increased in the co-culture supernatant of MHC- Ⅱ+ target cell group (all P<0.01). Conclusion: A co-culture model of LAG3+ Jurkat cells and tumor cells was successfully constructed in vitro. The anti-LAG3 antibody might increase the killing effect of Jurkat cells against MGC-803 and A549 tumor cells through blocking LAG3/MHC-Ⅱ interaction, which may be related to the increased secretion levels of cytokines IL-2, IL-10 and TNF-α in the supernatant of co-culture system.
Objective: The co-culture model of LAG3+ Jurkat cells and tumor cells was constructed to investigate the anti-tumor effect and mechanism of a novel fully human anti-LAG3 monoclonal antibody in vitro. Methods: Jurkat cells were stimulated with PHA to simulate TIL, and the secretion of IL-2 was detected by ELISA to evaluate the degree of Jurkat cell activation. Meanwhile, FCM, Immunofluorescence and WB assays were employed to detect the expression of LAG3 in activated Jurkat cells and MHC classⅡ molecule（MHC-Ⅱ）, a LAG3 ligand, in HGC-27, MGC-803 and A549 tumor cells. The co-culture model of activated LAG3+ Jurkat cells and tumor cells was constructed, and CCK-8 assays were employed to detect the killing efficiency of LAG3+ Jurkat cells against tumor cells at different effector-target ratios and the effect of the anti-LAG3 antibody . The secretion levels of cytokines IL-2, IL-10 and TNF-α in supernatant of co-culture system were detected by ELISA. Results: After 48 h treatment, 2 μg/mL PHA exhibited no obvious cytotoxicity to Jurkat cells (P>0.05), but could significantly induce IL-2 secretion (P<0.01) and LAG3 expression (P<0.01), indicating activated LAG3+ Jurkat cells were acquired. MGC-803 and A549 cells significantly expressed MHC-Ⅱ (P<0.01), but HGC-27 cells did not express MHC-Ⅱ (P>0.05). The co-culture model of LAG3+ Jurkat cells and tumor cells was constructed at a effector-target ratio of 10∶1. The anti-LAG3 antibody could effectively enhance the killing efficiency of Jurkat cells against MHC-Ⅱ+ tumor cells (P<0.05). Further analysis revealed that the secretion levels of cytokines IL-2, IL-10 and TNF-α were increased in the co-culture supernatant of MHC- Ⅱ+ target cell group (all P<0.01). Conclusion: A co-culture model of LAG3+ Jurkat cells and tumor cells was successfully constructed in vitro. The anti-LAG3 antibody might increase the killing effect of Jurkat cells against MGC-803 and A549 tumor cells through blocking LAG3/MHC-Ⅱ interaction, which may be related to the increased secretion levels of cytokines IL-2, IL-10 and TNF-α in the supernatant of co-culture system.
2022, 29(5):426-433.
DOI: 10.3872/j.issn.1007-385X.2022.05.006
Abstract:
Objective: To investigate the function and mechanism of ferroptosis in the radiation resistance of colorectal tumor-repopulating cells. Methods: Human colorectal tumor cells HCT116 (defined as Control cells) were cultured in two-dimensional normal conditions, and tumor regenerative cells with high tumorigenicity (defined as TRCs) were cultured and screened in threedimensional fibrin soft gels by the mechanical force method. Both the control group and TRC group cells were exposed to X-rays with different doses (2, 4, 6, 8 Gy) and MTS and the clone formation assay were used tomeasure the cell viability rate and proliferation ability. After the Control cells and TRCs were treated with ferroptosis inducer (Erastin) and X-rays respectively, they were stained with C11-BODIPY reagent, and the lipid peroxidation level of the cells was observed and determined by confocal microscopy and flow cytometry. qPCR was used to determine the effects of Erastin and X-rays treatments on the expressions of ferroptosis-related genes glutathione peroxidase 4 (GPX4) and acyl-coenzyme A synthetase long-chain family member 4 (ACSL4) in the Control cells and TRCs; WB assay was performed to determine the effects on the expressions of ferroptosis-related proteins GPX4 and ACSL4. Results: Colorectal TRCs with high stemness were cultured and screened out from soft fibrin gels. After irradiation with different doses (2, 4, 6, 8 Gy) of X-rays, the viability rate, the clone sizeand the number of clones in the control group were significantly lower than those in the TRC group (all P<0.05). After the cells in the control group were irradiated with different doses of X-rays (4, 8 Gy) and treated with Erastin, the lipid peroxidation level of the cells in the X-ray treated group was significantly higher than that in the untreated group (P<0.05). The lipid peroxidation level of the cells in the Erastin-treated group was significantly higher than that in the DMSO-treated group (P<0.05). There was no statistical difference among all treatment subgroups in the TRC group (all P>0.05). The mechanism study indicated that compared with those in control cells, GPX4 and ACSL4 in TRCs under ferroptosis-inducing conditions (X-ray radiation and Erastin treatment) presented expressions that contributed more to radiation resistance, i. e., continued upregulation of GPX4 and downregulation of ACSL4 and their expressions were dependent on the doses of Erastin. Conclusion: Colorectal TRCs may resist ferroptosis through a high expression of GPX4 and a low expression of ACSL4, which in turn induces radiation resistance.
Objective: To investigate the function and mechanism of ferroptosis in the radiation resistance of colorectal tumor-repopulating cells. Methods: Human colorectal tumor cells HCT116 (defined as Control cells) were cultured in two-dimensional normal conditions, and tumor regenerative cells with high tumorigenicity (defined as TRCs) were cultured and screened in threedimensional fibrin soft gels by the mechanical force method. Both the control group and TRC group cells were exposed to X-rays with different doses (2, 4, 6, 8 Gy) and MTS and the clone formation assay were used tomeasure the cell viability rate and proliferation ability. After the Control cells and TRCs were treated with ferroptosis inducer (Erastin) and X-rays respectively, they were stained with C11-BODIPY reagent, and the lipid peroxidation level of the cells was observed and determined by confocal microscopy and flow cytometry. qPCR was used to determine the effects of Erastin and X-rays treatments on the expressions of ferroptosis-related genes glutathione peroxidase 4 (GPX4) and acyl-coenzyme A synthetase long-chain family member 4 (ACSL4) in the Control cells and TRCs; WB assay was performed to determine the effects on the expressions of ferroptosis-related proteins GPX4 and ACSL4. Results: Colorectal TRCs with high stemness were cultured and screened out from soft fibrin gels. After irradiation with different doses (2, 4, 6, 8 Gy) of X-rays, the viability rate, the clone sizeand the number of clones in the control group were significantly lower than those in the TRC group (all P<0.05). After the cells in the control group were irradiated with different doses of X-rays (4, 8 Gy) and treated with Erastin, the lipid peroxidation level of the cells in the X-ray treated group was significantly higher than that in the untreated group (P<0.05). The lipid peroxidation level of the cells in the Erastin-treated group was significantly higher than that in the DMSO-treated group (P<0.05). There was no statistical difference among all treatment subgroups in the TRC group (all P>0.05). The mechanism study indicated that compared with those in control cells, GPX4 and ACSL4 in TRCs under ferroptosis-inducing conditions (X-ray radiation and Erastin treatment) presented expressions that contributed more to radiation resistance, i. e., continued upregulation of GPX4 and downregulation of ACSL4 and their expressions were dependent on the doses of Erastin. Conclusion: Colorectal TRCs may resist ferroptosis through a high expression of GPX4 and a low expression of ACSL4, which in turn induces radiation resistance.
2022, 29(5):434-441.
DOI: 10.3872/j.issn.1007-385X.2022.05.007
Abstract:
Objective: To investigate the effects of long non-coding RNA (lncRNA) taurine up-regulated gene 1 (TUG1) on the proliferation, apoptosis, and epithelial-mesenchymal transition (EMT) of papillary thyroid carcinoma (PTC) cells and its mechanism. Methods: Real-time fluorescent quantitative PCR (qPCR) was used to detect the expression of lncRNA TUG1 in 35 pairs of PTC tissue and corresponding paracancerous tissue specimens that were surgically resected in Tangshan Workers’Hospital, Hebei Province from May 2019 to April 2021, human PTC cell lines (TPC-1, BHP10-3, K1, SW1736) and human normal thyroid epithelial Nthyori 3-1 cells. TPC-1 cells were cultured in vitro and divided into control group, si-NC group, si-TUG1 group, miR-NC group, miR-524-5p mimic group, si-TUG1+NC inhibitor group, si-TUG1+miR-524-5p inhibitor group, miR-524-5p mimic+pc-DNA group, and miR-524-5p mimic+ pcDNA BRAF (V-raf murine sarcoma viral oncogene homolog B1) group by transfecting corresponding vectors. CCK-8 and FCM methods were used to detect the proliferation and apoptosis of TPC-1 cells, WB method was used to detect the expression of BRAF, proliferating cell nuclear antigen (PCNA), cysteine protease-3 (Caspase-3), E-cadherin, N-cadherin and vimentin in TPC-1 cells, and the dual-luciferase reporter gene experiment was used to verify the targeting relationship between miR-524-5p and lncRNA TUG1 as well as BRAF. Results: lncRNA TUG1 was up-regulated in PTC tissues and cells (P<0.05). Silencing the expression of lncRNA TUG1 or up-regulating the expression of miR-524-5p could significantly inhibit the proliferation and EMT, and promote apoptosis of TPC-1 cells (all P<0.05). Dual-luciferase reporter gene experiment showed that there was a targeting relationship between miR-524-5p and lncRNA TUG1 as well as between miR-524-5p and BRAF (all P<0.05). Silencing the expression of miR-524-5p could reverse the effects of lncRNA TUG1 knockdown on inhibiting proliferation and EMT and promoting apoptosis of TPC-1 cells (all P<0.05), and up-regulation of BRAF expression could reverse the effects of miR-524-5p overexpression on inhibiting proliferation, EMT and promoting apoptosis of TPC-1 cell (all P<0.05). Conclusion: lncRNA TUG1 is up-regulated in PTC tissues and TPC-1 cells. Silencing the expression of lncRNA TUG1 can inhibit proliferation and EMT but promote cell apoptosis of PTC cells by regulating the miR-524-5p/BRAF axis.
Objective: To investigate the effects of long non-coding RNA (lncRNA) taurine up-regulated gene 1 (TUG1) on the proliferation, apoptosis, and epithelial-mesenchymal transition (EMT) of papillary thyroid carcinoma (PTC) cells and its mechanism. Methods: Real-time fluorescent quantitative PCR (qPCR) was used to detect the expression of lncRNA TUG1 in 35 pairs of PTC tissue and corresponding paracancerous tissue specimens that were surgically resected in Tangshan Workers’Hospital, Hebei Province from May 2019 to April 2021, human PTC cell lines (TPC-1, BHP10-3, K1, SW1736) and human normal thyroid epithelial Nthyori 3-1 cells. TPC-1 cells were cultured in vitro and divided into control group, si-NC group, si-TUG1 group, miR-NC group, miR-524-5p mimic group, si-TUG1+NC inhibitor group, si-TUG1+miR-524-5p inhibitor group, miR-524-5p mimic+pc-DNA group, and miR-524-5p mimic+ pcDNA BRAF (V-raf murine sarcoma viral oncogene homolog B1) group by transfecting corresponding vectors. CCK-8 and FCM methods were used to detect the proliferation and apoptosis of TPC-1 cells, WB method was used to detect the expression of BRAF, proliferating cell nuclear antigen (PCNA), cysteine protease-3 (Caspase-3), E-cadherin, N-cadherin and vimentin in TPC-1 cells, and the dual-luciferase reporter gene experiment was used to verify the targeting relationship between miR-524-5p and lncRNA TUG1 as well as BRAF. Results: lncRNA TUG1 was up-regulated in PTC tissues and cells (P<0.05). Silencing the expression of lncRNA TUG1 or up-regulating the expression of miR-524-5p could significantly inhibit the proliferation and EMT, and promote apoptosis of TPC-1 cells (all P<0.05). Dual-luciferase reporter gene experiment showed that there was a targeting relationship between miR-524-5p and lncRNA TUG1 as well as between miR-524-5p and BRAF (all P<0.05). Silencing the expression of miR-524-5p could reverse the effects of lncRNA TUG1 knockdown on inhibiting proliferation and EMT and promoting apoptosis of TPC-1 cells (all P<0.05), and up-regulation of BRAF expression could reverse the effects of miR-524-5p overexpression on inhibiting proliferation, EMT and promoting apoptosis of TPC-1 cell (all P<0.05). Conclusion: lncRNA TUG1 is up-regulated in PTC tissues and TPC-1 cells. Silencing the expression of lncRNA TUG1 can inhibit proliferation and EMT but promote cell apoptosis of PTC cells by regulating the miR-524-5p/BRAF axis.
2022, 29(5):442-448.
DOI: 10.3872/j.issn.1007-385X.2022.05.008
Abstract:
Objective：To investigate the expression of ITGB2 (integrinβ2) in renal cell carcinoma (RCC) tissues and cells (ACHN cells) and its effects on the proliferation, migration, invasion and cell cycle of ACHN cells. Methods: The expression level of ITGB2 in RCC tissues and para-cancerous tissues was analyzed by GEPIA database. The tissue samples of 66 RCC patients retained in the biological specimen bank of the Fourth Hospital of Hebei Medical University from 2016 to 2020 were selected for this study. The expression level of ITGB2 in 66 cases of RCC tissues and para-cancerous tissues was detected by immunohistochemical SP and qPCR, and the relationship between ITGB2 and clinical parameters was analyzed. The shRNA with ITGB2 knockdown was constructed and transfected into ACHN cells for functional experiments to detect its effect on the malignant biological behaviors of ACHN cells, and its effect on the cell cycle was detected by flow cytometry. WB was used to detect the effect of ITGB2 knockdown on ITGB2 protein expression in ACHN cells. Results: The relative expression of ITGB2 in RCC tissues was significantly higher than that in para-cancerous tissue (P<0.01), and the expression was related to the clinical stage of RCC (P<0.05). Transfection of shITGB2 into ACHN cells could knock down the gene and protein expression of ITGB2 (all P<0.01). Knockdown of ITGB2 could significantly inhibit the proliferation (P<0.05), migration(P<0.01) and invasion (P<0.05) of ACHN cells but had no significant effect on cell cycle (P>0.05). Conclusion: ITGB2 is highly expressed in RCC tissues and cells and is associated with the clinical stage of RCC. Knockdown of ITGB2 can inhibit the malignant biological behaviors of ACHN cells.
Objective：To investigate the expression of ITGB2 (integrinβ2) in renal cell carcinoma (RCC) tissues and cells (ACHN cells) and its effects on the proliferation, migration, invasion and cell cycle of ACHN cells. Methods: The expression level of ITGB2 in RCC tissues and para-cancerous tissues was analyzed by GEPIA database. The tissue samples of 66 RCC patients retained in the biological specimen bank of the Fourth Hospital of Hebei Medical University from 2016 to 2020 were selected for this study. The expression level of ITGB2 in 66 cases of RCC tissues and para-cancerous tissues was detected by immunohistochemical SP and qPCR, and the relationship between ITGB2 and clinical parameters was analyzed. The shRNA with ITGB2 knockdown was constructed and transfected into ACHN cells for functional experiments to detect its effect on the malignant biological behaviors of ACHN cells, and its effect on the cell cycle was detected by flow cytometry. WB was used to detect the effect of ITGB2 knockdown on ITGB2 protein expression in ACHN cells. Results: The relative expression of ITGB2 in RCC tissues was significantly higher than that in para-cancerous tissue (P<0.01), and the expression was related to the clinical stage of RCC (P<0.05). Transfection of shITGB2 into ACHN cells could knock down the gene and protein expression of ITGB2 (all P<0.01). Knockdown of ITGB2 could significantly inhibit the proliferation (P<0.05), migration(P<0.01) and invasion (P<0.05) of ACHN cells but had no significant effect on cell cycle (P>0.05). Conclusion: ITGB2 is highly expressed in RCC tissues and cells and is associated with the clinical stage of RCC. Knockdown of ITGB2 can inhibit the malignant biological behaviors of ACHN cells.
2022, 29(5):449-455.
DOI: 10.3872/j.issn.1007-385X.2022.05.009
Abstract:
Objective: To investigate the effects of long non-coding RNA zinc finger antisense 1 (lncRNA ZFAS1) on the proliferation, invasion, and migration of liver cancer cells by regulating the miR-588/high mobility group AT-hook protein 2 (HMGA2) axis. Methods: Real-time fluorescent quantitative PCR (qRT-PCR) and western blot were performed to measure the expression levels of ZFAS1, miR-588 and HMGA2 in 80 pairs of liver cancer tissues and corresponding para-cancerous issues (the tissue sample were collected from Shouyi Campus, Wuhan Third Hospital during Jan. 2018 and Dec. 2019), human normal liver cell line (LO2) and liver cancer cell lines (HepG2, Huh7, HCCLM3). The survival of patients was analyzed using the Kaplan-Meier survival curve. HepG2 cells were divided into blank group, si-NC group, si-ZFAS1 group, si-ZFAS1+inhibitor NC group, and si-ZFAS1+miR-588 inhibitor group. qPCR was performed to measure the expression of ZFAS1 and miR-588 in HepG2 cells of each group, and Western blot was performed to measure the expression of HMGA2 protein in the cells. CCK-8 method, Transwell, and scratch test were performed to measure the proliferation, invasion, and migration of HepG2 cells. Dual-luciferase reporter gene experiment was performed to verify the targeting relationship between ZFAS1 and miR-588 as well as between miR-588 and HMGA2. A HepG2 cell transplanted tumor model was established in nude mice to examine the effect of silencing ZFAS1 or/and miR-588 on the growth of transplanted tumors. Results: ZFAS1 and HMGA2 were highly expressed while miR-588 was lowly expressed in liver cancer tissues and liver cancer cells (all P<0.05). The 2-year survival rate of patients with low ZFAS1 expression was higher than that in the high expression group (P<0.05). Compared with the blank group, the relative expression of ZFAS1 and HMGA2 protein in the si-ZFAS1 group was significantly reduced, and the relative expression of miR-588 was significantly increased (all P<0.05); compared with the si-ZFAS1 group, the relative expression of ZFAS1 in the si-ZFAS1+miR-588 inhibitor group did not change significantly (P>0.05), however, the relative expression of HMGA2 protein was significantly increased, and the relative expression of miR-588 was significantly reduced (P<0.05). Silencing ZFAS1 was able to inhibit the proliferation, invasion, and migration of HepG2 cells and inhibit the growth of transplanted tumors in nude mice (all P<0.05). ZFAS1 targeted and down-regulated the expression of miR-588, while miR-588 targeted and down-regulated the expression of HMGA2. Simultaneous inhibition of miR-588 expression could reverse the inhibitory effects of silencing ZFAS1 on the proliferation, invasion, and migration of HepG2 cells and the growth of transplanted tumors in nude mice (all P<0.05). Conclusion: Silencing ZFAS1 may down-regulate the expression of HMGA2 by promoting the expression of miR-588, thereby inhibiting the proliferation, invasion, and migration of liver cancer HepG2 cells.
Objective: To investigate the effects of long non-coding RNA zinc finger antisense 1 (lncRNA ZFAS1) on the proliferation, invasion, and migration of liver cancer cells by regulating the miR-588/high mobility group AT-hook protein 2 (HMGA2) axis. Methods: Real-time fluorescent quantitative PCR (qRT-PCR) and western blot were performed to measure the expression levels of ZFAS1, miR-588 and HMGA2 in 80 pairs of liver cancer tissues and corresponding para-cancerous issues (the tissue sample were collected from Shouyi Campus, Wuhan Third Hospital during Jan. 2018 and Dec. 2019), human normal liver cell line (LO2) and liver cancer cell lines (HepG2, Huh7, HCCLM3). The survival of patients was analyzed using the Kaplan-Meier survival curve. HepG2 cells were divided into blank group, si-NC group, si-ZFAS1 group, si-ZFAS1+inhibitor NC group, and si-ZFAS1+miR-588 inhibitor group. qPCR was performed to measure the expression of ZFAS1 and miR-588 in HepG2 cells of each group, and Western blot was performed to measure the expression of HMGA2 protein in the cells. CCK-8 method, Transwell, and scratch test were performed to measure the proliferation, invasion, and migration of HepG2 cells. Dual-luciferase reporter gene experiment was performed to verify the targeting relationship between ZFAS1 and miR-588 as well as between miR-588 and HMGA2. A HepG2 cell transplanted tumor model was established in nude mice to examine the effect of silencing ZFAS1 or/and miR-588 on the growth of transplanted tumors. Results: ZFAS1 and HMGA2 were highly expressed while miR-588 was lowly expressed in liver cancer tissues and liver cancer cells (all P<0.05). The 2-year survival rate of patients with low ZFAS1 expression was higher than that in the high expression group (P<0.05). Compared with the blank group, the relative expression of ZFAS1 and HMGA2 protein in the si-ZFAS1 group was significantly reduced, and the relative expression of miR-588 was significantly increased (all P<0.05); compared with the si-ZFAS1 group, the relative expression of ZFAS1 in the si-ZFAS1+miR-588 inhibitor group did not change significantly (P>0.05), however, the relative expression of HMGA2 protein was significantly increased, and the relative expression of miR-588 was significantly reduced (P<0.05). Silencing ZFAS1 was able to inhibit the proliferation, invasion, and migration of HepG2 cells and inhibit the growth of transplanted tumors in nude mice (all P<0.05). ZFAS1 targeted and down-regulated the expression of miR-588, while miR-588 targeted and down-regulated the expression of HMGA2. Simultaneous inhibition of miR-588 expression could reverse the inhibitory effects of silencing ZFAS1 on the proliferation, invasion, and migration of HepG2 cells and the growth of transplanted tumors in nude mice (all P<0.05). Conclusion: Silencing ZFAS1 may down-regulate the expression of HMGA2 by promoting the expression of miR-588, thereby inhibiting the proliferation, invasion, and migration of liver cancer HepG2 cells.
2022, 29(5):456-463.
DOI: 10.3872/j.issn.1007-385X.2022.05.010
Abstract:
Objective: To explore the relationship between cerebral endothelial cell adhesion molecule (CERCAM) and prognosis of colon cancer patients, so as to establish a nomogram with good prognostic value by using Cox model and verify its diagnostic value. Methods: The expression profile of CERCAM in colon cancer tissues and normal tissues as well as clinicopathologic data of colon cancer patients were downloaded from TCGA and GTEx databases. At the same time, colon cancer and paracancerous tissue samples collected from 4 colon cancer patients admitted to Nanjing First Hospital from Feburary 2013 to June 2019 were used for verification. Firstly, differential analysis, pathway enrichment analysis, and survival analysis were performed to investigate the tissue localization, functional and prognostic value of CERCAM expression. In addition, Cox regression analyses was conducted to screen the risk factors for the prognosis of colon cancer. A nomogram was established based on CERCAM and various risk factors, and was verified and evaluated by concordance indices, calibration curves, and time-dependent receiver operating characteristic (ROC) curves. In addition, the survival curves were plotted according to risk stratification. Results: The expression of CERCAM in colon cancer tissues was significantly lower than that in normal tissues (P<0.001). The overall survival (P=0.032) and survival status (P=0.002) of colon cancer patients with high CERCAM expression level was significantly inferior to those with low CERCAM expression level. CERCAM was correlated with the activation of proteoglycans in cancer and PI3K-Akt signaling pathway. Cox analysis showed that CERCAM expression level (HR=2.22, P=0.015), T stage (HR=5.65, P=0.015), M stage (HR=2.62, P=0.022) were independent risk factors for prognosis of colon cancer, while vascular infiltration (HR=2.30, P=0.089) was a risk factor as well. Based on the above factors, a nomogram was established. The concordance indices suggested good discrimination of the nomogram, and the training set was consistent with the test set. The calibration curves and ROC curves also indicated good predictive ability of the nomogram. Survival curves plotted according to risk stratification suggested that the high-risk group had lower survival rates (P<0.000 1). Conclusion: High level CERCAM expression is correlated with the poor prognosis of colon cancer patients, which is possibly associated with proteoglycans in cancer and PI3K-Akt signal pathway. The nomogram established based on CERCAM is superior to the traditional prediction model, which has certain clinical value in predicting survival prognosis of colon cancer patients. This practical model is helpful for the risk stratification and the optimization of treatment plan.
Objective: To explore the relationship between cerebral endothelial cell adhesion molecule (CERCAM) and prognosis of colon cancer patients, so as to establish a nomogram with good prognostic value by using Cox model and verify its diagnostic value. Methods: The expression profile of CERCAM in colon cancer tissues and normal tissues as well as clinicopathologic data of colon cancer patients were downloaded from TCGA and GTEx databases. At the same time, colon cancer and paracancerous tissue samples collected from 4 colon cancer patients admitted to Nanjing First Hospital from Feburary 2013 to June 2019 were used for verification. Firstly, differential analysis, pathway enrichment analysis, and survival analysis were performed to investigate the tissue localization, functional and prognostic value of CERCAM expression. In addition, Cox regression analyses was conducted to screen the risk factors for the prognosis of colon cancer. A nomogram was established based on CERCAM and various risk factors, and was verified and evaluated by concordance indices, calibration curves, and time-dependent receiver operating characteristic (ROC) curves. In addition, the survival curves were plotted according to risk stratification. Results: The expression of CERCAM in colon cancer tissues was significantly lower than that in normal tissues (P<0.001). The overall survival (P=0.032) and survival status (P=0.002) of colon cancer patients with high CERCAM expression level was significantly inferior to those with low CERCAM expression level. CERCAM was correlated with the activation of proteoglycans in cancer and PI3K-Akt signaling pathway. Cox analysis showed that CERCAM expression level (HR=2.22, P=0.015), T stage (HR=5.65, P=0.015), M stage (HR=2.62, P=0.022) were independent risk factors for prognosis of colon cancer, while vascular infiltration (HR=2.30, P=0.089) was a risk factor as well. Based on the above factors, a nomogram was established. The concordance indices suggested good discrimination of the nomogram, and the training set was consistent with the test set. The calibration curves and ROC curves also indicated good predictive ability of the nomogram. Survival curves plotted according to risk stratification suggested that the high-risk group had lower survival rates (P<0.000 1). Conclusion: High level CERCAM expression is correlated with the poor prognosis of colon cancer patients, which is possibly associated with proteoglycans in cancer and PI3K-Akt signal pathway. The nomogram established based on CERCAM is superior to the traditional prediction model, which has certain clinical value in predicting survival prognosis of colon cancer patients. This practical model is helpful for the risk stratification and the optimization of treatment plan.
2022, 29(5):464-471.
DOI: 10.3872/j.issn.1007-385X.2022.05.011
Abstract:
Objective: To systematically evaluate the efficacy and safety of nivolumab plus ipilimumab versus nivolumab monotherapy in the treatment of malignant tumors, so as to provide evidence-based medical proof for clinical administration. Methods: Databases, such as PubMed, CNKI, VIP, and Wanfang Data, were searched from January 2000 to January 2022 to collect the clinical trial data in terms of nivolumab plus ipilimumab versus nivolumab monotherapy for malignant tumors were published in both domestic and abroad. Two reviewers independently evaluated the quality of included RCTs, and extracted and cross-checked the data. RevMan 5. 4 was used for the Meta-analysis. Results: A total of 7 RCTs studies including 10 articles were included. Compared with the nivolumab monotherapy group, the OS of patients in the combined treatment group was significantly improved (HR=0.86, 95% CI: 0. 75-0.99, P=0. 03), and the PFS was significantly prolonged (HR=0.69, 95% CI: 0.55-0.85, P=0.000 6). However, as for safety, treatment-related adverse events (OR=3.18, 95% CI: 1.55-6.55, P=0.002) and adverse events leading to drug discontinuation (OR=7.11, 95% CI: 4.85-10.42, P<0.000 01) in the combination therapy group were significantly higher than those in the monotherapy group. Conclusion: Compared with nivolumab monotherapy, nivolumab plus ipilimumab can significantly improve the OS and PFS of tumor patients, but is also associated with more treatment-related adverse events and adverse events leading to drug discontinuation. Therefore, it is necessary to pay attention to follow-up and regular monitoring to prevent the occurrence of serious adverse reactions.
Objective: To systematically evaluate the efficacy and safety of nivolumab plus ipilimumab versus nivolumab monotherapy in the treatment of malignant tumors, so as to provide evidence-based medical proof for clinical administration. Methods: Databases, such as PubMed, CNKI, VIP, and Wanfang Data, were searched from January 2000 to January 2022 to collect the clinical trial data in terms of nivolumab plus ipilimumab versus nivolumab monotherapy for malignant tumors were published in both domestic and abroad. Two reviewers independently evaluated the quality of included RCTs, and extracted and cross-checked the data. RevMan 5. 4 was used for the Meta-analysis. Results: A total of 7 RCTs studies including 10 articles were included. Compared with the nivolumab monotherapy group, the OS of patients in the combined treatment group was significantly improved (HR=0.86, 95% CI: 0. 75-0.99, P=0. 03), and the PFS was significantly prolonged (HR=0.69, 95% CI: 0.55-0.85, P=0.000 6). However, as for safety, treatment-related adverse events (OR=3.18, 95% CI: 1.55-6.55, P=0.002) and adverse events leading to drug discontinuation (OR=7.11, 95% CI: 4.85-10.42, P<0.000 01) in the combination therapy group were significantly higher than those in the monotherapy group. Conclusion: Compared with nivolumab monotherapy, nivolumab plus ipilimumab can significantly improve the OS and PFS of tumor patients, but is also associated with more treatment-related adverse events and adverse events leading to drug discontinuation. Therefore, it is necessary to pay attention to follow-up and regular monitoring to prevent the occurrence of serious adverse reactions.
2022, 29(5):472-477.
DOI: 10.3872/j.issn.1007-385X.2022.05.012
Abstract:
免疫检查点抑制剂及CAR-T细胞的基础及临床转化研究已成为肿瘤研究的热点之一。免疫治疗已在多种类型的肿瘤中应用，并可观察到持续的应答和显著的生存优势，但仍有部分患者并未受益，如何对免疫治疗疗效进行有效的预测，是亟待解决的问题。单细胞测序技术是在单个细胞水平上，对基因组、转录组、表观组进行高通量测序，揭示单个细胞的基因结构和基因表达状态，反映细胞间的异质性，破解多种类型肿瘤的免疫微环境及外周血循环免疫细胞的亚型及图谱，分析肿瘤细胞及肿瘤微环境的异质性，在发掘新的疾病诊断标志物、分辨细胞亚型、治疗靶标及在个体化治疗方面具有独特的优势。
免疫检查点抑制剂及CAR-T细胞的基础及临床转化研究已成为肿瘤研究的热点之一。免疫治疗已在多种类型的肿瘤中应用，并可观察到持续的应答和显著的生存优势，但仍有部分患者并未受益，如何对免疫治疗疗效进行有效的预测，是亟待解决的问题。单细胞测序技术是在单个细胞水平上，对基因组、转录组、表观组进行高通量测序，揭示单个细胞的基因结构和基因表达状态，反映细胞间的异质性，破解多种类型肿瘤的免疫微环境及外周血循环免疫细胞的亚型及图谱，分析肿瘤细胞及肿瘤微环境的异质性，在发掘新的疾病诊断标志物、分辨细胞亚型、治疗靶标及在个体化治疗方面具有独特的优势。
2022, 29(5):478-482.
DOI: 10.3872/j.issn.1007-385X.2022.05.013
Abstract:
醛缩酶家族是糖酵解过程中的第4种酶，其家族成员ALDOA、ALDOB和ALDOC被发现在消化、呼吸、泌尿等系统的恶性肿瘤中差异表达，与肿瘤患者预后密切相关，有望成为的独立的预后标志物。醛缩酶家族成员可通过影响细胞代谢促进肿瘤细胞增殖，也可通过非酶功能促进肿瘤细胞侵袭转移，还可通过多种机制介导肿瘤耐药。由于醛缩酶家族在肿瘤发生发展中的重要作用，其不仅可以作为肿瘤诊断及监测预后的标志物，还有望成为肿瘤治疗的新靶点，可为肿瘤的预测、诊断及治疗提供临床应用价值。
醛缩酶家族是糖酵解过程中的第4种酶，其家族成员ALDOA、ALDOB和ALDOC被发现在消化、呼吸、泌尿等系统的恶性肿瘤中差异表达，与肿瘤患者预后密切相关，有望成为的独立的预后标志物。醛缩酶家族成员可通过影响细胞代谢促进肿瘤细胞增殖，也可通过非酶功能促进肿瘤细胞侵袭转移，还可通过多种机制介导肿瘤耐药。由于醛缩酶家族在肿瘤发生发展中的重要作用，其不仅可以作为肿瘤诊断及监测预后的标志物，还有望成为肿瘤治疗的新靶点，可为肿瘤的预测、诊断及治疗提供临床应用价值。
2022, 29(5):483-488.
DOI: 10.3872/j.issn.1007-385X.2022.05.014
Abstract:
多聚腺苷二磷酸核糖聚合酶（PARP）抑制剂是治疗转移性去势抵抗性前列腺癌（mCRPC）的新型靶向药物，其对DNA损伤修复基因突变的mCRPC患者具有较高的药物敏感性，多项临床试验结果显示，PARP抑制剂单一疗法及联合疗法在mCRPC患者中具有明显优势，有望为mCRPC患者个体化、精准化治疗带来希望。然而，PARP抑制剂治疗仍有许多问题需纳入考虑，如安全性、耐药性等。对PARP抑制剂在mCRPC中的作用机制及相关临床研究现状进行讨论，可为mCRPC患者提供新的治疗思路。
多聚腺苷二磷酸核糖聚合酶（PARP）抑制剂是治疗转移性去势抵抗性前列腺癌（mCRPC）的新型靶向药物，其对DNA损伤修复基因突变的mCRPC患者具有较高的药物敏感性，多项临床试验结果显示，PARP抑制剂单一疗法及联合疗法在mCRPC患者中具有明显优势，有望为mCRPC患者个体化、精准化治疗带来希望。然而，PARP抑制剂治疗仍有许多问题需纳入考虑，如安全性、耐药性等。对PARP抑制剂在mCRPC中的作用机制及相关临床研究现状进行讨论，可为mCRPC患者提供新的治疗思路。
2022, 29(5):489-496.
DOI: 10.3872/j.issn.1007-385X.2022.05.015
Abstract:
免疫检查点抑制剂（ICI）是一种备受关注的肿瘤免疫治疗手段，可通过阻断免疫检查点信号转导来恢复甚至增强T淋巴细胞的抗肿瘤免疫反应以达到抗肿瘤的治疗目的。PD-L1表达水平或可作为派姆单抗的一线使用标准；较高的肿瘤突变负荷（TMB）增加癌细胞抗原表达，使后者易被免疫细胞监视定位并清除，被定义为预测ICI疗效的生物标志物；错配修复基因（MMR）与MSI具有高度一致性，在多种实体瘤中具有预后预测作用；肿瘤浸润淋巴细胞联合TNM分期评估非小细胞肺癌患者预后准确性甚至优于病理标准，通过检测炎症因子的基因表达水平评估T细胞炎症基因表达谱可预测ICI的治疗效果；体细胞突变状态与免疫治疗的预后有关；低水平的中性/淋巴细胞比值（NLR）可能是免疫相关不良事件发生的独立预测因素；肠道微生物通过影响TIL水平干预免疫治疗的效果；除此以外还有其他预测因素可供参考。梳理总结预测相关标志物，分析其价值性与局限性，可为临床选择适合患者的治疗方案，也可使患者临床获益达到最大。
免疫检查点抑制剂（ICI）是一种备受关注的肿瘤免疫治疗手段，可通过阻断免疫检查点信号转导来恢复甚至增强T淋巴细胞的抗肿瘤免疫反应以达到抗肿瘤的治疗目的。PD-L1表达水平或可作为派姆单抗的一线使用标准；较高的肿瘤突变负荷（TMB）增加癌细胞抗原表达，使后者易被免疫细胞监视定位并清除，被定义为预测ICI疗效的生物标志物；错配修复基因（MMR）与MSI具有高度一致性，在多种实体瘤中具有预后预测作用；肿瘤浸润淋巴细胞联合TNM分期评估非小细胞肺癌患者预后准确性甚至优于病理标准，通过检测炎症因子的基因表达水平评估T细胞炎症基因表达谱可预测ICI的治疗效果；体细胞突变状态与免疫治疗的预后有关；低水平的中性/淋巴细胞比值（NLR）可能是免疫相关不良事件发生的独立预测因素；肠道微生物通过影响TIL水平干预免疫治疗的效果；除此以外还有其他预测因素可供参考。梳理总结预测相关标志物，分析其价值性与局限性，可为临床选择适合患者的治疗方案，也可使患者临床获益达到最大。
2022, 29(5):497-501.
DOI: 10.3872/j.issn.1007-385X.2022.05.016
Abstract:
趋化因子（C-X-C基序）配体1（CXCL1）是CXC趋化因子家族中的一员，在炎症形成、新血管生成和肿瘤形成中都具有重要功能。CXCL1可通过自分泌途径促进正常成纤维细胞转化为肿瘤相关成纤维细胞，还可通过VEGF、肿瘤相关巨噬细胞促进肿瘤血管生成。CXCL1诱导骨髓来源的抑制性细胞（MDSC）和肿瘤相关巨噬细胞（TAM）在肿瘤组织中的聚集，减少T细胞浸润，从而促进肿瘤细胞发送免疫逃逸。临床上，CXCL1不仅可用于恶性肿瘤辅助诊断和判断患者预后，更可能成为肿瘤生物治疗的干预靶点，对于CXCL1及其受体的调控可能会成为特异性治疗恶性肿瘤的一种重要策略。
趋化因子（C-X-C基序）配体1（CXCL1）是CXC趋化因子家族中的一员，在炎症形成、新血管生成和肿瘤形成中都具有重要功能。CXCL1可通过自分泌途径促进正常成纤维细胞转化为肿瘤相关成纤维细胞，还可通过VEGF、肿瘤相关巨噬细胞促进肿瘤血管生成。CXCL1诱导骨髓来源的抑制性细胞（MDSC）和肿瘤相关巨噬细胞（TAM）在肿瘤组织中的聚集，减少T细胞浸润，从而促进肿瘤细胞发送免疫逃逸。临床上，CXCL1不仅可用于恶性肿瘤辅助诊断和判断患者预后，更可能成为肿瘤生物治疗的干预靶点，对于CXCL1及其受体的调控可能会成为特异性治疗恶性肿瘤的一种重要策略。
2022, 29(5):502-504.
DOI: 10.3872/j.issn.1007-385X.2022.05.017
Abstract:
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- 《中国肿瘤生物治疗杂志》
- 1994年创刊
- 主办单位：Chinese Society of Immunology, Chinese Anti-cancer Association
- 邮编：200433
- 电话：021-81871002-22
- 电子邮箱：cjcb@biother.cn
- 网址:http://www.biother.cn
- 刊号：ISSN 1007-385X
- CN 31-1725/R
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.