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Volume 29,Issue 12,2022 Table of Contents
2022, 29(12):1057-1066.
DOI: 10.3872/j.issn.1007-385X.2022.12.001
Abstract:
Natural killer (NK) cells, a kind of innate lymphocyte with strong anti-tumor function, can quickly recognize and kill tumor cells. Their function is regulated by a variety of signals of activating and inhibitory receptors. However, the killing function of tumor-infiltrating NK cell is dysregulated due to the immunosuppressive tumor microenvironment, which may even promote the immune escape of tumor cells, resulting in poor clinical therapeutic effects of various immunotherapies. Up-regulated expression of inhibitory ligands on tumor cells, a large number of anti-inflammatory cytokines in the tumor microenvironment, abnormal hypoxia, low pH, and other indicators induced impaired killing function of tumor-infiltrating NK cells. In recent years, the research on tumor microenvironment and tumor infiltrating NK cells is at the forefront of tumor immunity, and many clinical research results have been achieved. Many studies have shown that tumor-infiltrating NK cells are usually characterized by up-regulation of inhibitory receptors, down-regulation of activating receptors, and abnormal metabolism. Based on this, researchers have developed many targeted therapies to restore the killing function of NK cells. In this paper, we summarize the characteristics of tumor-infiltrating NK cells and the related tumor immunotherapies based on the mechanisms of activation and inhibition of NK cell function.
Natural killer (NK) cells, a kind of innate lymphocyte with strong anti-tumor function, can quickly recognize and kill tumor cells. Their function is regulated by a variety of signals of activating and inhibitory receptors. However, the killing function of tumor-infiltrating NK cell is dysregulated due to the immunosuppressive tumor microenvironment, which may even promote the immune escape of tumor cells, resulting in poor clinical therapeutic effects of various immunotherapies. Up-regulated expression of inhibitory ligands on tumor cells, a large number of anti-inflammatory cytokines in the tumor microenvironment, abnormal hypoxia, low pH, and other indicators induced impaired killing function of tumor-infiltrating NK cells. In recent years, the research on tumor microenvironment and tumor infiltrating NK cells is at the forefront of tumor immunity, and many clinical research results have been achieved. Many studies have shown that tumor-infiltrating NK cells are usually characterized by up-regulation of inhibitory receptors, down-regulation of activating receptors, and abnormal metabolism. Based on this, researchers have developed many targeted therapies to restore the killing function of NK cells. In this paper, we summarize the characteristics of tumor-infiltrating NK cells and the related tumor immunotherapies based on the mechanisms of activation and inhibition of NK cell function.
2022, 29(12):1067-1075.
DOI: 10.3872/j.issn.1007-385X.2022.12.002
Abstract:
Natural killer group 2 member A (NKG2A) is an important immune checkpoint molecule on the surface of immune cells. The binding between NKG2A and its ligand HLA-E inhibits the immune function of NK cells and T cells, and even causes their functional exhaustion and leads to tumor escape. Anti-NKG2A antibody can restore the function of T cells and NK cells by blocking the binding of NKG2A to its ligand, thus awakening a strong antitumor efficacy. Compared with other immune checkpoint molecules, such as PD-1 and CTLA-4, NKG2A-blocking antibody has unique advantages in clinical oncology treatment. It blocks the identification of NKG2A and relevant signaling pathways and reverses the functional exhaustion of T cells and NK cells at the same time, fully awakening the strong anti-tumor immunity of the body. Currently, several clinical trials on NKG2A-based anti-tumor immunotherapy are ongoing, showing good safety and therapeutic efficacy. In this review, we summarize the expression and signal transduction of NKG2A and HLA-E, NKG2A-mediated functional exhaustion of immune cells, and current clinical research status, problems, and possible strategies of NKG2A-targeted tumor immunotherapy, to provide a reference for the development and clinical application of NKG2A-targeted tumor immunotherapy.
Natural killer group 2 member A (NKG2A) is an important immune checkpoint molecule on the surface of immune cells. The binding between NKG2A and its ligand HLA-E inhibits the immune function of NK cells and T cells, and even causes their functional exhaustion and leads to tumor escape. Anti-NKG2A antibody can restore the function of T cells and NK cells by blocking the binding of NKG2A to its ligand, thus awakening a strong antitumor efficacy. Compared with other immune checkpoint molecules, such as PD-1 and CTLA-4, NKG2A-blocking antibody has unique advantages in clinical oncology treatment. It blocks the identification of NKG2A and relevant signaling pathways and reverses the functional exhaustion of T cells and NK cells at the same time, fully awakening the strong anti-tumor immunity of the body. Currently, several clinical trials on NKG2A-based anti-tumor immunotherapy are ongoing, showing good safety and therapeutic efficacy. In this review, we summarize the expression and signal transduction of NKG2A and HLA-E, NKG2A-mediated functional exhaustion of immune cells, and current clinical research status, problems, and possible strategies of NKG2A-targeted tumor immunotherapy, to provide a reference for the development and clinical application of NKG2A-targeted tumor immunotherapy.
2022, 29(12):1076-1086.
DOI: 10.3872/j.issn.1007-385X.2022.12.003
Abstract:
Objective: To investigate the expression of methyltransferase-like 3 (METTL3) in esophageal squamous cell carcinoma (ESCC) tissue and cells and its effect on the glycolysis proliferation of ESCC cells as well as the potential molecular mechanisms. Methods: Based on the TCGA database, the expression of METTL3 and its possible enrichment pathway in ESCC were elucidated. Thirty-four ESCC tissues and corresponding paracancerous tissues were collected from surgical resections at the Affiliated Hospital of Beichuan Medical College between January 2021 and June 2021, the expression of METTL3 in ESCC tissues was verified by immunohistochemistry. The CCK-8 and colony formation assay were used to evaluate the change in the proliferation ability of ESCC cells after METTL3 knockdown. The expression level of m6A in total RNA of ESCC cells after METTL3 knockdown was detected by colorimetric method. Methylated RNA immunoprecipitation qPCR (MeRIP-qPCR) was used to detect the effect of METTL3 on the m6A modification level of glucose transporter 4 (GLUT4) mRNA. The biological mechanisms of METTL3 in the glycolysis metabolism of ESCC were evaluated using WB and qPCR. Results: The expression level of METTL3 was significantly increased in ESCC tissues as well as cell lines (all P<0.001). After the knockdown of METTL3, the proliferation ability of ESCC cells was significantly reduced, and the m6A modification level of total RNA was significantly reduced (all P<0.001). In addition, knockdown of METTL3 significantly inhibited the m6A modification level of GLUT4 mRNA in KYSE150 and TE-1 cells (all P<0.01), inhibited glucose uptake and lactate release by down-regulating GLUT4 expression (all P<0.01), and finally down-regulated the activity of mTORC1 pathway and inhibited the proliferation of ESCC cells. Moreover, a synergetic effect was found in METTL3-depleted ESCC cells combined with mTORC1 pathway inhibitor. Conclusion: METTL3-mediated m6A modification promotes glycolysis and proliferation of ESCC cells by regulating the GLUT4-mTORC1 signaling axis.
Objective: To investigate the expression of methyltransferase-like 3 (METTL3) in esophageal squamous cell carcinoma (ESCC) tissue and cells and its effect on the glycolysis proliferation of ESCC cells as well as the potential molecular mechanisms. Methods: Based on the TCGA database, the expression of METTL3 and its possible enrichment pathway in ESCC were elucidated. Thirty-four ESCC tissues and corresponding paracancerous tissues were collected from surgical resections at the Affiliated Hospital of Beichuan Medical College between January 2021 and June 2021, the expression of METTL3 in ESCC tissues was verified by immunohistochemistry. The CCK-8 and colony formation assay were used to evaluate the change in the proliferation ability of ESCC cells after METTL3 knockdown. The expression level of m6A in total RNA of ESCC cells after METTL3 knockdown was detected by colorimetric method. Methylated RNA immunoprecipitation qPCR (MeRIP-qPCR) was used to detect the effect of METTL3 on the m6A modification level of glucose transporter 4 (GLUT4) mRNA. The biological mechanisms of METTL3 in the glycolysis metabolism of ESCC were evaluated using WB and qPCR. Results: The expression level of METTL3 was significantly increased in ESCC tissues as well as cell lines (all P<0.001). After the knockdown of METTL3, the proliferation ability of ESCC cells was significantly reduced, and the m6A modification level of total RNA was significantly reduced (all P<0.001). In addition, knockdown of METTL3 significantly inhibited the m6A modification level of GLUT4 mRNA in KYSE150 and TE-1 cells (all P<0.01), inhibited glucose uptake and lactate release by down-regulating GLUT4 expression (all P<0.01), and finally down-regulated the activity of mTORC1 pathway and inhibited the proliferation of ESCC cells. Moreover, a synergetic effect was found in METTL3-depleted ESCC cells combined with mTORC1 pathway inhibitor. Conclusion: METTL3-mediated m6A modification promotes glycolysis and proliferation of ESCC cells by regulating the GLUT4-mTORC1 signaling axis.
2022, 29(12):1087-1093.
DOI: 10.3872/j.issn.1007-385X.2022.12.004
Abstract:
Objective: To analyze the expression of FOXD1 in esophageal squamous cell carcinoma (ESCC) and its relationship with clinicopathological features and prognosis. To investigate the effect of FOXD1 on the proliferation and invasion of TE1 cells and its effect on TGF- β1 induction of epithelial-mesenchymal transition (EMT). Methods: The expression of FOXD1 in ESCC tissues and cells was detected by qPCR and immunohistochemical method (IHC). The relationships between its expression level and clinicopathological characteristics and prognosis of patients were also analyzed. FOXD1 knockdown plasmid was constructed and transfected into TE1 cells to detect its effect on the proliferation and invasion of TE1 cells. qPCR and Western blotting were used to detect the expression levels of FOXD1 and EMT-related markers before and after TGF- β1 treatment and the effect of knockdown FOXD1 on the expression of EMT-related markers. Results: FOXD1 was highly expressed in ESCC tissues and cells (all P<0.01), and negatively correlated with the overall survival of patients. FOXD1 expression level, tumor TNM stage, and lymph node metastasis were independent factors affecting the prognosis of ESCC patients (all P<0.01). TGF-β1 treatment may raise the expression level of FOXD1 in TE1 cells and induce the expression of EMT-related markers (all P<0.05). Knockdown FOXD1 may suppress the proliferation and invasion ability of TE1 cells and can partially reverse the EMT process of TE1 cells induced by TGF-β1. Conclusion: FOXD1, highly expressed in ESCC tissues and TE1 cells, is an independent factor affecting the prognosis of ESCC patients. Knockdown of FOXD1 can significantly inhibit the proliferation, invasion and TGF-β1 mediated EMT process of TE1 cells.
Objective: To analyze the expression of FOXD1 in esophageal squamous cell carcinoma (ESCC) and its relationship with clinicopathological features and prognosis. To investigate the effect of FOXD1 on the proliferation and invasion of TE1 cells and its effect on TGF- β1 induction of epithelial-mesenchymal transition (EMT). Methods: The expression of FOXD1 in ESCC tissues and cells was detected by qPCR and immunohistochemical method (IHC). The relationships between its expression level and clinicopathological characteristics and prognosis of patients were also analyzed. FOXD1 knockdown plasmid was constructed and transfected into TE1 cells to detect its effect on the proliferation and invasion of TE1 cells. qPCR and Western blotting were used to detect the expression levels of FOXD1 and EMT-related markers before and after TGF- β1 treatment and the effect of knockdown FOXD1 on the expression of EMT-related markers. Results: FOXD1 was highly expressed in ESCC tissues and cells (all P<0.01), and negatively correlated with the overall survival of patients. FOXD1 expression level, tumor TNM stage, and lymph node metastasis were independent factors affecting the prognosis of ESCC patients (all P<0.01). TGF-β1 treatment may raise the expression level of FOXD1 in TE1 cells and induce the expression of EMT-related markers (all P<0.05). Knockdown FOXD1 may suppress the proliferation and invasion ability of TE1 cells and can partially reverse the EMT process of TE1 cells induced by TGF-β1. Conclusion: FOXD1, highly expressed in ESCC tissues and TE1 cells, is an independent factor affecting the prognosis of ESCC patients. Knockdown of FOXD1 can significantly inhibit the proliferation, invasion and TGF-β1 mediated EMT process of TE1 cells.
2022, 29(12):1094-1100.
DOI: 10.3872/j.issn.1007-385X.2022.12.005
Abstract:
Objective: To explore the role of miR-1-3p, a gastric cancer-related biomarker, on gastric cancer cell proliferation and its mechanism by bioinformatics approach. Methods: Transcriptomic data from gastric cancer (n=375) and paraneoplastic tissues (n=45) in the TCGA database were collected to construct a gastric cancer-specific mRNA-miRNA network, screen potential miRNA-like markers, predict the downstream target genes of the markers and analyze their functions using TargetScan. Human normal gastric epithelial cell and gastric cancer cell lines have been selected, and their miR-1-3p and myocardin (MYOCD expression was detected by qPCR. The miR-1-3p mimics were transfected into GES-1, AGS, and MKN45 cells using lipofectamine 2000. The proliferation ability of the cells was determined by CCK-8 assay, the expression of MYOCD was measured by WB assay, and the targeting relationship between miR-1-3p and MYOCD was verified by dual luciferase reporter assay. Results: Differentially expressed 259 miRNAs and 7 545 mRNAs were obtained by database data analysis to construct a regulatory network of gastric cancer-specific mRNA-miRNAs. Analysis of vulnerability structure in the network identified miR-1-3p as a potential gastric cancer marker, and in-depth analysis revealed its significance for the diagnosis and prognostic assessment of gastric cancer, while predicting MYOCD as its downstream target. Cellular assays showed that miR-1-3p was lowly expressed in gastric cancer cells (P<0.05); overexpression of miR-1-3p inhibited the proliferation ability of AGS and MKN-45 in gastric cancer cells (P<0.05 or P<0.01); and inhibited the expression of MYOCD (P<0.01); miR-1-3p was predicted to be associated with two binding sites in the 3'UTR region by the TargetScan database, and dual luciferase reporter assays showed that high expression of miR-1-3p at one of the wild-type predicted sites significantly inhibited MYOCD expression (P<0.01). Conclusion:miR-1-3p may be a potential diagnostic and prognostic-related marker for gastric cancer, and miR-1-3p may affect gastric cancer by targeting MYOCD.
Objective: To explore the role of miR-1-3p, a gastric cancer-related biomarker, on gastric cancer cell proliferation and its mechanism by bioinformatics approach. Methods: Transcriptomic data from gastric cancer (n=375) and paraneoplastic tissues (n=45) in the TCGA database were collected to construct a gastric cancer-specific mRNA-miRNA network, screen potential miRNA-like markers, predict the downstream target genes of the markers and analyze their functions using TargetScan. Human normal gastric epithelial cell and gastric cancer cell lines have been selected, and their miR-1-3p and myocardin (MYOCD expression was detected by qPCR. The miR-1-3p mimics were transfected into GES-1, AGS, and MKN45 cells using lipofectamine 2000. The proliferation ability of the cells was determined by CCK-8 assay, the expression of MYOCD was measured by WB assay, and the targeting relationship between miR-1-3p and MYOCD was verified by dual luciferase reporter assay. Results: Differentially expressed 259 miRNAs and 7 545 mRNAs were obtained by database data analysis to construct a regulatory network of gastric cancer-specific mRNA-miRNAs. Analysis of vulnerability structure in the network identified miR-1-3p as a potential gastric cancer marker, and in-depth analysis revealed its significance for the diagnosis and prognostic assessment of gastric cancer, while predicting MYOCD as its downstream target. Cellular assays showed that miR-1-3p was lowly expressed in gastric cancer cells (P<0.05); overexpression of miR-1-3p inhibited the proliferation ability of AGS and MKN-45 in gastric cancer cells (P<0.05 or P<0.01); and inhibited the expression of MYOCD (P<0.01); miR-1-3p was predicted to be associated with two binding sites in the 3'UTR region by the TargetScan database, and dual luciferase reporter assays showed that high expression of miR-1-3p at one of the wild-type predicted sites significantly inhibited MYOCD expression (P<0.01). Conclusion:miR-1-3p may be a potential diagnostic and prognostic-related marker for gastric cancer, and miR-1-3p may affect gastric cancer by targeting MYOCD.
2022, 29(12):1101-1107.
DOI: 10.3872/j.issn.1007-385X.2022.12.006
Abstract:
Objective: To investigate the effects of circFBXL5 on the proliferation, migration, and invasion of bladder cancer T24 cells by targeting miR-515-5p and its possible molecular mechanisms. Methods: 41 bladder cancer tissues and their adjacent tissues were collected at Suzhou Hospital of Integrated Traditional Chinese and Western Medicine from April 2020 to June 2020. The expressions of circFBXL5 and miR-515-5p were detected by qPCR. Dual-luciferase reporter assay was used to verify the targeting relationship between circFBXL5 and miR-515-5p. Human bladder cancer cells T24 were cultured in vitro and divided into si-NC group, si-circFBXL5 group, anti-miR-NC+si-circFBXL5 group, and si-circFBXL5+anti-miR-515-5p group. MTT assay, plate colony formation assay, flow cytometry, Transwell assay and Western blotting were used to detect cell proliferation, clone formation, migration, invasion, apoptosis and BAX and Bcl-2 protein levels of T24 cells after transfection, respectively. Results: circFBXL5 was highly expressed and miR-515-5p was lowly expressed in bladder cancer tissues (all P<0.05). circFBXL5 could negatively regulate the expression of miR-515-5p. After the knockdown of circFBXL5, the cell proliferation inhibition rate, apoptosis rate, and protein level of BAX were significantly increased (all P<0.05); the number of cell clone formation, migration, and invasion cells were decreased (all P<0.05); the protein level of Bcl-2 was significantly decreased (P <0.05). Knockdown of circFBXL5 and miR-515-5p simultaneously could partially reverse the inhibiting effect of circFBXL5 knockdown on T24 cells. Conclusion: circFBXL5 promoted the proliferation, migration, and invasion of bladder cancer T24 cells by inhibiting miR-515-5p expression. circFBXL5 and miR-515-5p may serve as potential molecular targets for bladder cancer treatment.
Objective: To investigate the effects of circFBXL5 on the proliferation, migration, and invasion of bladder cancer T24 cells by targeting miR-515-5p and its possible molecular mechanisms. Methods: 41 bladder cancer tissues and their adjacent tissues were collected at Suzhou Hospital of Integrated Traditional Chinese and Western Medicine from April 2020 to June 2020. The expressions of circFBXL5 and miR-515-5p were detected by qPCR. Dual-luciferase reporter assay was used to verify the targeting relationship between circFBXL5 and miR-515-5p. Human bladder cancer cells T24 were cultured in vitro and divided into si-NC group, si-circFBXL5 group, anti-miR-NC+si-circFBXL5 group, and si-circFBXL5+anti-miR-515-5p group. MTT assay, plate colony formation assay, flow cytometry, Transwell assay and Western blotting were used to detect cell proliferation, clone formation, migration, invasion, apoptosis and BAX and Bcl-2 protein levels of T24 cells after transfection, respectively. Results: circFBXL5 was highly expressed and miR-515-5p was lowly expressed in bladder cancer tissues (all P<0.05). circFBXL5 could negatively regulate the expression of miR-515-5p. After the knockdown of circFBXL5, the cell proliferation inhibition rate, apoptosis rate, and protein level of BAX were significantly increased (all P<0.05); the number of cell clone formation, migration, and invasion cells were decreased (all P<0.05); the protein level of Bcl-2 was significantly decreased (P <0.05). Knockdown of circFBXL5 and miR-515-5p simultaneously could partially reverse the inhibiting effect of circFBXL5 knockdown on T24 cells. Conclusion: circFBXL5 promoted the proliferation, migration, and invasion of bladder cancer T24 cells by inhibiting miR-515-5p expression. circFBXL5 and miR-515-5p may serve as potential molecular targets for bladder cancer treatment.
2022, 29(12):1108-1114.
DOI: 10.3872/j.issn.1007-385X.2022.12.007
Abstract:
Objective: To investigate the distribution of CD68+ tumor-associated macrophages (TAM), CD8+ T cells, Foxp3+ Treg cells, and other immune cells infiltrating lung adenocarcinoma (LUAD) tissues and their associations with patient prognosis. Methods: Ninety-three cases of LUAD tissues and 78 cases of paraneoplastic tissues surgically resected at the Third Affiliated Hospital of Soochow University between September 2004 and April 2009 were collected. The immune cell infiltration and distribution were detected by tissue microarray (TMA) and multiplex immunofluorescence (mIF) techniques. The Wilcoxon rank sum test was used to compare the differences in infiltration levels between cancer and paraneoplastic tissues, and between cancer nests and interstitial tissues. χ2 test was employed to analyze the relationship between their infiltration levels, CD8+/CD68+ cell ratios and clinicopathological features. Kaplan-Meier method and COX model were used to analyze the potential risk factors affecting patients' OS. Results: The infiltration levels of CD68+ TAM, CD8+ T cells, and Foxp3+ Treg cells in cancer tissues were significantly higher than those in paraneoplastic tissues (all P<0.01) while the infiltration levels of CD68+ TAM and CD8+ T cells in the interstitial tissues were significantly higher than that in the cancer nests (all P<0.01). The levels of total CD68+ TAM, cancer nest and interstitial CD68+ TAM infiltration were positively correlated with lymph node metastasis (all P<0.05); the levels of CD68+ TAM infiltration in cancer nests were positively correlated with T stage (P<0.05), and the levels of interstitial CD68+ TAM infiltration were positively correlated with pathological grading (P<0.05); the CD8+/CD68+ cell ratio in cancer tissues was negatively correlated with pathological grading and lymph node metastasis (all P<0.05). Kaplan-Meier survival analysis showed that the OS of patients with high infiltration of total CD68+ TAM, cancer nests and interstitial CD68+ TAM in LUAD tissues was shorter than that of patients with low infiltration (P<0.05 or P<0.01), and the OS of patients with high CD8+/CD68+ cell ratio in cancer tissues was significantly longer than that of patients with low ratio (P<0.05). Multivariate COX model analysis showed that age, TNM stage and CD8+/CD68+ cell ratio in cancer tissues were independent risk factors for the prognosis of LUAD patients (P<0.05 or P<0.01). Conclusion: Highly infiltrative CD68+ TAM was significantly associated with the progression, invasion, metastasis and poor prognosis of LUAD, and a high CD8+/CD68+ cell ratio was an independent protective factor for the OS of patients with LUAD.
Objective: To investigate the distribution of CD68+ tumor-associated macrophages (TAM), CD8+ T cells, Foxp3+ Treg cells, and other immune cells infiltrating lung adenocarcinoma (LUAD) tissues and their associations with patient prognosis. Methods: Ninety-three cases of LUAD tissues and 78 cases of paraneoplastic tissues surgically resected at the Third Affiliated Hospital of Soochow University between September 2004 and April 2009 were collected. The immune cell infiltration and distribution were detected by tissue microarray (TMA) and multiplex immunofluorescence (mIF) techniques. The Wilcoxon rank sum test was used to compare the differences in infiltration levels between cancer and paraneoplastic tissues, and between cancer nests and interstitial tissues. χ2 test was employed to analyze the relationship between their infiltration levels, CD8+/CD68+ cell ratios and clinicopathological features. Kaplan-Meier method and COX model were used to analyze the potential risk factors affecting patients' OS. Results: The infiltration levels of CD68+ TAM, CD8+ T cells, and Foxp3+ Treg cells in cancer tissues were significantly higher than those in paraneoplastic tissues (all P<0.01) while the infiltration levels of CD68+ TAM and CD8+ T cells in the interstitial tissues were significantly higher than that in the cancer nests (all P<0.01). The levels of total CD68+ TAM, cancer nest and interstitial CD68+ TAM infiltration were positively correlated with lymph node metastasis (all P<0.05); the levels of CD68+ TAM infiltration in cancer nests were positively correlated with T stage (P<0.05), and the levels of interstitial CD68+ TAM infiltration were positively correlated with pathological grading (P<0.05); the CD8+/CD68+ cell ratio in cancer tissues was negatively correlated with pathological grading and lymph node metastasis (all P<0.05). Kaplan-Meier survival analysis showed that the OS of patients with high infiltration of total CD68+ TAM, cancer nests and interstitial CD68+ TAM in LUAD tissues was shorter than that of patients with low infiltration (P<0.05 or P<0.01), and the OS of patients with high CD8+/CD68+ cell ratio in cancer tissues was significantly longer than that of patients with low ratio (P<0.05). Multivariate COX model analysis showed that age, TNM stage and CD8+/CD68+ cell ratio in cancer tissues were independent risk factors for the prognosis of LUAD patients (P<0.05 or P<0.01). Conclusion: Highly infiltrative CD68+ TAM was significantly associated with the progression, invasion, metastasis and poor prognosis of LUAD, and a high CD8+/CD68+ cell ratio was an independent protective factor for the OS of patients with LUAD.
2022, 29(12):1115-1124.
DOI: 10.3872/j.issn.1007-385X.2022.12.008
Abstract:
Objective: To investigate the expression and methylation level of epidermal growth factor, latrophilin and seven transmembrane domain-containing 1 (ELTD1) in clear cell renal cell carcinoma (ccRCC) and their correlation with the clinicopathological features and prognosis of patients. Methods: The differential expression and methylation of ELTD1 gene were analyzed with open databases to discuss the correlation between the ELTD1 expression and the clinicopathological characteristics and prognosis of patients. TIMER 2.0 database was adopted to analyze the tumor immune cell infiltration of ccRCC and screen out ELTD1-related immune checkpoint genes. GO function enrichment and KEGG pathway enrichment analysis were also performed. The genes closely related to ELTD1 were identified through gene co-expression analysis. Results: ELTD1 was significantly upregulated in ccRCC (P<0.05), whose expression is negatively correlated with its methylation in TCGA-KIRC (R=-0.37, P<0.01). ELTD1 transcription expression was significantly correlated with age, T stage, M stage and grade (all P<0.01). Higher expression of ELTD1 was closely associated with overall survival (OS) (HR=0.55, P<0.01) and progression-free survival (PFS) (HR=0.63, P<0.01). Upregulation of ELTD1 expression was an independent protective factor in ccRCC. ELTD1 expression was significantly correlated with immune infiltrating of B cells (R=-0.16, P<0.01), CD4+ T cells (R=-0.27, P<0.01), CD8+ T cells (R=-0.25, P<0.01), macrophages (R=-0.31, P<0.01) and neutrophils (R=-0.27, P<0.001), and diverse immune checkpoint genes (all P<0.01). GO function and KEGG pathway enrichment analysis showed that vascular process and tumor-related signaling pathways were enriched in the ELTD1 high expression phenotypes (all P<0.01). Gene co-expression analysis showed that the effect of tumor inhibition was related to the co-expression network. Conclusion: Upregulation of ELTD1 expression and lower methylation level of ELTD1 in ccRCC are indicators of better prognosis and are related to tumor immune infiltration.
Objective: To investigate the expression and methylation level of epidermal growth factor, latrophilin and seven transmembrane domain-containing 1 (ELTD1) in clear cell renal cell carcinoma (ccRCC) and their correlation with the clinicopathological features and prognosis of patients. Methods: The differential expression and methylation of ELTD1 gene were analyzed with open databases to discuss the correlation between the ELTD1 expression and the clinicopathological characteristics and prognosis of patients. TIMER 2.0 database was adopted to analyze the tumor immune cell infiltration of ccRCC and screen out ELTD1-related immune checkpoint genes. GO function enrichment and KEGG pathway enrichment analysis were also performed. The genes closely related to ELTD1 were identified through gene co-expression analysis. Results: ELTD1 was significantly upregulated in ccRCC (P<0.05), whose expression is negatively correlated with its methylation in TCGA-KIRC (R=-0.37, P<0.01). ELTD1 transcription expression was significantly correlated with age, T stage, M stage and grade (all P<0.01). Higher expression of ELTD1 was closely associated with overall survival (OS) (HR=0.55, P<0.01) and progression-free survival (PFS) (HR=0.63, P<0.01). Upregulation of ELTD1 expression was an independent protective factor in ccRCC. ELTD1 expression was significantly correlated with immune infiltrating of B cells (R=-0.16, P<0.01), CD4+ T cells (R=-0.27, P<0.01), CD8+ T cells (R=-0.25, P<0.01), macrophages (R=-0.31, P<0.01) and neutrophils (R=-0.27, P<0.001), and diverse immune checkpoint genes (all P<0.01). GO function and KEGG pathway enrichment analysis showed that vascular process and tumor-related signaling pathways were enriched in the ELTD1 high expression phenotypes (all P<0.01). Gene co-expression analysis showed that the effect of tumor inhibition was related to the co-expression network. Conclusion: Upregulation of ELTD1 expression and lower methylation level of ELTD1 in ccRCC are indicators of better prognosis and are related to tumor immune infiltration.
2022, 29(12):1125-1129.
DOI: 10.3872/j.issn.1007-385X.2022.12.009
Abstract:
Objective: To examine the efficacy and safety of lienal polypeptide injection combined with FOLFOX4 or XELOX in the treatment of stage Ⅲ/Ⅳ colon cancer. Methods: One hundred and sixty patients who underwent a curative resection of colon cancer in the Sixth People's Hospital of Huizhou between January 2017 and June 2020 were included in the study. All patients were randomized into 2 groups of 80 each: patients who received lienal polypeptide injection combined with FOLFOX4 (lienal polypeptide + FOLFOX4 group) and patients who received lienal polypeptide injection combined with XELOX (lienal polypeptide + XELOX group). All patients were given six rounds of treatment. Two-year follow-up assessments of the clinical efficacy, immunity, nutritional status, quality of life and toxicity or adverse effects were conducted 1 months after the end of treatment. Results: Compared with the lienal polypeptide + FOLFOX4 group, the disease control rate (DCR) and objective response rate (ORR) of the lienal polypeptide+XELOX group were dramatically improved (all P<0.05). The percentage of CD3+ T cells, CD4+ T cells and NK cells, the EORTC QLQ-C30 scores and the level of PNI in the lienal polypeptide+XELOX group were higher (all P<0.05). NLR, LMR, CA125, CA199, and CEA were significantly decreased (all P<0.05). In terms of adverse effects, the incidence of leukopenia, neutropenia, neurotoxicity, oral mucositis, and hand foot syndrome in the lienal polypeptide + XELOX group were remarkably decreased compared with the lienal polypeptide + FOLFOX4 group (all P<0.05). No difference in progression-free survival (PFS) and overall survival (OS) was detectable (all P>0.05). Conclusion: Compared with lienal polypeptide injection combined with FOLFOX4, lienal polypeptide injection combined with XELOX has a significant advantage in decreasing the incidence of adverse events and improving the quality of life of Ⅲ/Ⅳ colon cancer patients.
Objective: To examine the efficacy and safety of lienal polypeptide injection combined with FOLFOX4 or XELOX in the treatment of stage Ⅲ/Ⅳ colon cancer. Methods: One hundred and sixty patients who underwent a curative resection of colon cancer in the Sixth People's Hospital of Huizhou between January 2017 and June 2020 were included in the study. All patients were randomized into 2 groups of 80 each: patients who received lienal polypeptide injection combined with FOLFOX4 (lienal polypeptide + FOLFOX4 group) and patients who received lienal polypeptide injection combined with XELOX (lienal polypeptide + XELOX group). All patients were given six rounds of treatment. Two-year follow-up assessments of the clinical efficacy, immunity, nutritional status, quality of life and toxicity or adverse effects were conducted 1 months after the end of treatment. Results: Compared with the lienal polypeptide + FOLFOX4 group, the disease control rate (DCR) and objective response rate (ORR) of the lienal polypeptide+XELOX group were dramatically improved (all P<0.05). The percentage of CD3+ T cells, CD4+ T cells and NK cells, the EORTC QLQ-C30 scores and the level of PNI in the lienal polypeptide+XELOX group were higher (all P<0.05). NLR, LMR, CA125, CA199, and CEA were significantly decreased (all P<0.05). In terms of adverse effects, the incidence of leukopenia, neutropenia, neurotoxicity, oral mucositis, and hand foot syndrome in the lienal polypeptide + XELOX group were remarkably decreased compared with the lienal polypeptide + FOLFOX4 group (all P<0.05). No difference in progression-free survival (PFS) and overall survival (OS) was detectable (all P>0.05). Conclusion: Compared with lienal polypeptide injection combined with FOLFOX4, lienal polypeptide injection combined with XELOX has a significant advantage in decreasing the incidence of adverse events and improving the quality of life of Ⅲ/Ⅳ colon cancer patients.
2022, 29(12):1130-1135.
DOI: 10.3872/j.issn.1007-385X.2022.12.010
Abstract:
免疫检查点（IC）分子CTLA-4 和PD-1/PD-L1 的发现是肿瘤免疫治疗领域的重大突破。既往对IC 受体与配体相互作 用的认识通常基于反式作用，即受体和配体分别在不同细胞的细胞膜上表达。越来越多的研究结果揭示，肿瘤微环境中DC 的细 胞膜上同时表达的PD-L1 与CD80 之间的顺式作用在抗肿瘤免疫反应过程中具有重要意义。DC 细胞膜上的PD-L1 与CD80 形成 顺式异二聚体之后，其中的PD-L1 不能再与T 细胞膜上的PD-1 结合，但其中的CD80 却仍可以活化T 细胞膜上的CD28。更重要 的是，PD-L1:CD80 顺式异二聚体对T 细胞PD-1 和CD28 活化能力的这种差异直接关系到肿瘤对于不同的免疫检查点抑制剂（ICI）的反应。
免疫检查点（IC）分子CTLA-4 和PD-1/PD-L1 的发现是肿瘤免疫治疗领域的重大突破。既往对IC 受体与配体相互作 用的认识通常基于反式作用，即受体和配体分别在不同细胞的细胞膜上表达。越来越多的研究结果揭示，肿瘤微环境中DC 的细 胞膜上同时表达的PD-L1 与CD80 之间的顺式作用在抗肿瘤免疫反应过程中具有重要意义。DC 细胞膜上的PD-L1 与CD80 形成 顺式异二聚体之后，其中的PD-L1 不能再与T 细胞膜上的PD-1 结合，但其中的CD80 却仍可以活化T 细胞膜上的CD28。更重要 的是，PD-L1:CD80 顺式异二聚体对T 细胞PD-1 和CD28 活化能力的这种差异直接关系到肿瘤对于不同的免疫检查点抑制剂（ICI）的反应。
2022, 29(12):1136-1141.
DOI: 10.3872/j.issn.1007-385X.2022.12.011
Abstract:
潜伏期相关核抗原（LANA）是卡波西肉瘤相关疱疹病毒（KSHV）关键致癌蛋白，在卡波西肉瘤（KS）的多种致病途径 中发挥重要作用，包括参与KSHV 与宿主基因共复制、协助建立KSHV 基因组表观遗传修饰、调节KSHV 潜伏和裂解生命周期、 协助宿主细胞逃避免疫监视、促进肿瘤血管生成、调节宿主细胞代谢等，通过影响KSHV 和宿主细胞重编程促进KS 的发生发展。 LANA 不仅可作为临床检测KSHV 感染的免疫组织化学标志物，更有作为治疗靶点的潜在价值，目前已开展多项靶向LANA 的 研究，其中利用CRISPR/Cas9 技术靶向编码LANA 的ORF73 基因、以结构为基础筛选及合成的LANA 结合位点小分子抑制剂和 LANA 调节因子抑制剂在相关细胞和动物实验中显示出对KSHV 相关恶性肿瘤的治疗潜力，针对LANA 的靶点干预可能为及 KSHV 相关恶性肿瘤抗病毒治疗的新策略。
潜伏期相关核抗原（LANA）是卡波西肉瘤相关疱疹病毒（KSHV）关键致癌蛋白，在卡波西肉瘤（KS）的多种致病途径 中发挥重要作用，包括参与KSHV 与宿主基因共复制、协助建立KSHV 基因组表观遗传修饰、调节KSHV 潜伏和裂解生命周期、 协助宿主细胞逃避免疫监视、促进肿瘤血管生成、调节宿主细胞代谢等，通过影响KSHV 和宿主细胞重编程促进KS 的发生发展。 LANA 不仅可作为临床检测KSHV 感染的免疫组织化学标志物，更有作为治疗靶点的潜在价值，目前已开展多项靶向LANA 的 研究，其中利用CRISPR/Cas9 技术靶向编码LANA 的ORF73 基因、以结构为基础筛选及合成的LANA 结合位点小分子抑制剂和 LANA 调节因子抑制剂在相关细胞和动物实验中显示出对KSHV 相关恶性肿瘤的治疗潜力，针对LANA 的靶点干预可能为及 KSHV 相关恶性肿瘤抗病毒治疗的新策略。
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- 《中国肿瘤生物治疗杂志》
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.