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Volume 31,Issue 1,2024 Table of Contents
2024, 31(1):1-9.
DOI: 10.3872/j.issn.1007-385X.2024.01.001
Abstract:
Immune cell therapy has become a new therapeutic method for tumors by repairing the immune system and stimulating the immune function of patients, and it has been proved to have good safety and favorable therapeutic effects in some tumor patients. This paper focuses on the clinical safety and effectiveness of immune cell therapies including CAR-T cells, TCR-T cells, NK cells and TIL,etc. in tumor treatment at home and abroad in recent years. At the same time, from three aspects of technology, industrialization and policy, we put forward the key problems, challenges and corresponding solutions in the field of immune cell therapy in China, including the strengthening of original basic theoretical research, the application and transformation of new technologies, the standardization of cell product preparation and clinical research, the improvement of automated and industrialized cell production process systems, the guarantee of upstream products in the cell therapy industry, the cultivation and expansion of high-level scientific research and clinical research teams with strong innovation ability, and the establishment and improvement of policies, regulations and scientific supervision system that are compatible with the development of cell therapy technology. Solving of these problems can ensure the benign development of immune cell therapy in China.
Immune cell therapy has become a new therapeutic method for tumors by repairing the immune system and stimulating the immune function of patients, and it has been proved to have good safety and favorable therapeutic effects in some tumor patients. This paper focuses on the clinical safety and effectiveness of immune cell therapies including CAR-T cells, TCR-T cells, NK cells and TIL,etc. in tumor treatment at home and abroad in recent years. At the same time, from three aspects of technology, industrialization and policy, we put forward the key problems, challenges and corresponding solutions in the field of immune cell therapy in China, including the strengthening of original basic theoretical research, the application and transformation of new technologies, the standardization of cell product preparation and clinical research, the improvement of automated and industrialized cell production process systems, the guarantee of upstream products in the cell therapy industry, the cultivation and expansion of high-level scientific research and clinical research teams with strong innovation ability, and the establishment and improvement of policies, regulations and scientific supervision system that are compatible with the development of cell therapy technology. Solving of these problems can ensure the benign development of immune cell therapy in China.
2 The key to precise targeted immunotherapy for tumors: T cell receptor antigen screening techniques
2024, 31(1):10-18.
DOI: 10.3872/j.issn.1007-385X.2024.01.002
Abstract:
Adoptive T cell therapy has shown promising prospects in solid tumors and is becoming a major focus in the field of cancer therapy. TCR-T therapy relies on the specific recognition of peptide-major histocompatibility complex (pMHC) by the T cell receptor (TCR), leading to the activation of anti-tumor immune response of adoptive T cells. Therefore, a comprehensive analysis of the information of antigens targeted by TCRs is crucial for improving the efficacy and safety of TCR-T therapy in clinical applications. However, the lack of rapid and high-throughput TCR antigen screening techniques has limited the development of TCR-T therapy. In recent years, with the rapid advancement of high-throughput sequencing technologies, mass spectrometry-based flow cytometry, and computational biology, researchers have developed various TCR antigen screening techniques to decipher the antigen-targeting information of TCRs. This review summarizes TCR antigen screening methods, categorizing them into antigen-directed screening methods, TCR-directed screening methods, and bidirectional screening methods, and systematically introduces their strengths and limitations. Moreover, it delves into the prospects of TCR antigen screening development and provides new insights into the future of this area.
Adoptive T cell therapy has shown promising prospects in solid tumors and is becoming a major focus in the field of cancer therapy. TCR-T therapy relies on the specific recognition of peptide-major histocompatibility complex (pMHC) by the T cell receptor (TCR), leading to the activation of anti-tumor immune response of adoptive T cells. Therefore, a comprehensive analysis of the information of antigens targeted by TCRs is crucial for improving the efficacy and safety of TCR-T therapy in clinical applications. However, the lack of rapid and high-throughput TCR antigen screening techniques has limited the development of TCR-T therapy. In recent years, with the rapid advancement of high-throughput sequencing technologies, mass spectrometry-based flow cytometry, and computational biology, researchers have developed various TCR antigen screening techniques to decipher the antigen-targeting information of TCRs. This review summarizes TCR antigen screening methods, categorizing them into antigen-directed screening methods, TCR-directed screening methods, and bidirectional screening methods, and systematically introduces their strengths and limitations. Moreover, it delves into the prospects of TCR antigen screening development and provides new insights into the future of this area.
2024, 31(1):19-26.
DOI: 10.3872/j.issn.1007-385X.2024.01.003
Abstract:
Objective: To investigate the role of IL-22/IL-22RA1 (IL-22 receptor A1) pathway in the malignant progression of oral squamous cell carcinoma (OSCC) and the underlying mechanisms. Methods: The expression levels of IL-22RA1 in OSCC tissues and paired para-cancerous tissues were analyzed using the GEO database and immunohistochemistry. The association between IL-22RA1 expression and the clinicopathological characteristics of OSCC patients was detected and analyzed by tissue microarray immunohistochemistry. The relationship between IL-22RA1 expression and the prognosis of OSCC patients was analyzed using the EBI ArrayExpress database. The expression of IL-22 and IL-22RA1 in OSCC tissues was examined by immunofluorescence, and their association was also analyzed. IL-22RA1 expression was knocked down in OSCC WSU-HN4 and CAL27 cells by RNA interference technology, and the efficiency was verified using qPCR. The effects of IL-22 on the colonogenesis and migration of OSCC cells in the negative control (siNC) group and IL-22RA1 knock-down (siIL-22RA1) group were determined by plate cloning and transwell assays, respectively. The effects of IL-22 on the expression of IL-22RA1 and the phosphorylation level of STAT1, STAT3 and ERK1/2 in OSCC cells were detected using the WB assay. Results: The mRNA expression of IL-22RA1 in OSCC tissues was significantly higher than that in para-cancerous tissues (P<0.05). The expression of IL-22RA1 was associated with tumor size (P<0.05), lymph node metastasis (P<0.01), and poor prognosis (P<0.05) of OSCC patients. There was no significant correlation between the expression levels of IL-22 and IL-22RA1 in OSCC tissues, and IL-22 did not affect on the expression level of IL-22RA1 in OSCC cells (all P>0.05). IL-22 significantly enhanced the colony formation and migration abilities (all P<0.01) of OSCC cells, and activated STAT1, STAT3 and ERK1/2 signals in OSCC cells. After knocking down IL-22RA1 in OSCC cells, IL-22 could not exert the above effects. Conclusion: IL-22/IL-22RA1 can promote the growth and metastasis of OSCC by regulating cell proliferation and migration, and the downstream mechanism may be the activation of ERK1/2-STAT1/3 signaling pathway.
Objective: To investigate the role of IL-22/IL-22RA1 (IL-22 receptor A1) pathway in the malignant progression of oral squamous cell carcinoma (OSCC) and the underlying mechanisms. Methods: The expression levels of IL-22RA1 in OSCC tissues and paired para-cancerous tissues were analyzed using the GEO database and immunohistochemistry. The association between IL-22RA1 expression and the clinicopathological characteristics of OSCC patients was detected and analyzed by tissue microarray immunohistochemistry. The relationship between IL-22RA1 expression and the prognosis of OSCC patients was analyzed using the EBI ArrayExpress database. The expression of IL-22 and IL-22RA1 in OSCC tissues was examined by immunofluorescence, and their association was also analyzed. IL-22RA1 expression was knocked down in OSCC WSU-HN4 and CAL27 cells by RNA interference technology, and the efficiency was verified using qPCR. The effects of IL-22 on the colonogenesis and migration of OSCC cells in the negative control (siNC) group and IL-22RA1 knock-down (siIL-22RA1) group were determined by plate cloning and transwell assays, respectively. The effects of IL-22 on the expression of IL-22RA1 and the phosphorylation level of STAT1, STAT3 and ERK1/2 in OSCC cells were detected using the WB assay. Results: The mRNA expression of IL-22RA1 in OSCC tissues was significantly higher than that in para-cancerous tissues (P<0.05). The expression of IL-22RA1 was associated with tumor size (P<0.05), lymph node metastasis (P<0.01), and poor prognosis (P<0.05) of OSCC patients. There was no significant correlation between the expression levels of IL-22 and IL-22RA1 in OSCC tissues, and IL-22 did not affect on the expression level of IL-22RA1 in OSCC cells (all P>0.05). IL-22 significantly enhanced the colony formation and migration abilities (all P<0.01) of OSCC cells, and activated STAT1, STAT3 and ERK1/2 signals in OSCC cells. After knocking down IL-22RA1 in OSCC cells, IL-22 could not exert the above effects. Conclusion: IL-22/IL-22RA1 can promote the growth and metastasis of OSCC by regulating cell proliferation and migration, and the downstream mechanism may be the activation of ERK1/2-STAT1/3 signaling pathway.
2024, 31(1):27-31.
DOI: 10.3872/j.issn.1007-385X.2024.01.004
Abstract:
Objective: To investigate the effect of oncolytic Newcastle disease virus (NDV) on the proliferation, migration and invasion of human glioblastoma U87MG cells induced by IL-6 and its possible mechanism. Methods: U87MG cells were divided into control group, IL-6 group, NDV group and NDV+IL-6 group. The cells in IL-6 group and NDV+IL-6 group were pretreated with 75 ng/mL IL-6 for 1 h, and the other groups were pretreated with DMEM for 1 h; then, the four groups were treated with DMEM, 75 ng/mL IL-6, 1 Hu NDV, 1 Hu NDV+75 ng/mL IL-6 for 24 h, respectively. MTT assay, cell scratch test and Transwell invasion test were used to detect the effects of NDV and IL-6 on the proliferation, migration and invasion of U87MG cells, respectively. The protein expression levels of JAK2,p-JAK2, STAT3, p-STAT3 and MMP2 were detected by WB method. Results: Compared with the control group, the migration rate and number of invasive cells in IL-6 group were significantly increased (P<0.05 or P<0.01). Compared with IL-6 group, the proliferation rate of U87MG cells in NDV+IL-6 group was significantly decreased (P<0.05), and the migration rate and the number of invasive cells were significantly decreased (all P<0.01). WB results showed that compared with the control group, the p-STAT3/STAT3 ratio in IL-6 group was significantly increased (P<0.01), while the p-JAK2/JAK2 ratio, p-STAT3/STAT3 ratio and MMP-2 protein in NDV group were significantly decreased (P<0.05 or P<0.01); compared with IL-6 group, the p-STAT3/STAT3 ratio and the protein expression of MMP-2 in NDV+IL-6 group were significantly decreased (all P<0.05). Conclusion: NDV can inhibit IL-6 induced migration and invasion of human glioblastoma U87MG cells, and its mechanism may be related to its regulation of JAK2/STAT3 signaling pathway.
Objective: To investigate the effect of oncolytic Newcastle disease virus (NDV) on the proliferation, migration and invasion of human glioblastoma U87MG cells induced by IL-6 and its possible mechanism. Methods: U87MG cells were divided into control group, IL-6 group, NDV group and NDV+IL-6 group. The cells in IL-6 group and NDV+IL-6 group were pretreated with 75 ng/mL IL-6 for 1 h, and the other groups were pretreated with DMEM for 1 h; then, the four groups were treated with DMEM, 75 ng/mL IL-6, 1 Hu NDV, 1 Hu NDV+75 ng/mL IL-6 for 24 h, respectively. MTT assay, cell scratch test and Transwell invasion test were used to detect the effects of NDV and IL-6 on the proliferation, migration and invasion of U87MG cells, respectively. The protein expression levels of JAK2,p-JAK2, STAT3, p-STAT3 and MMP2 were detected by WB method. Results: Compared with the control group, the migration rate and number of invasive cells in IL-6 group were significantly increased (P<0.05 or P<0.01). Compared with IL-6 group, the proliferation rate of U87MG cells in NDV+IL-6 group was significantly decreased (P<0.05), and the migration rate and the number of invasive cells were significantly decreased (all P<0.01). WB results showed that compared with the control group, the p-STAT3/STAT3 ratio in IL-6 group was significantly increased (P<0.01), while the p-JAK2/JAK2 ratio, p-STAT3/STAT3 ratio and MMP-2 protein in NDV group were significantly decreased (P<0.05 or P<0.01); compared with IL-6 group, the p-STAT3/STAT3 ratio and the protein expression of MMP-2 in NDV+IL-6 group were significantly decreased (all P<0.05). Conclusion: NDV can inhibit IL-6 induced migration and invasion of human glioblastoma U87MG cells, and its mechanism may be related to its regulation of JAK2/STAT3 signaling pathway.
2024, 31(1):32-39.
DOI: 10.3872/j.issn.1007-385X.2024.01.005
Abstract:
Objective: To investigate whether sphingomyelin synthase 2 (SMS2) regulates the proliferation, migration, invasion and apoptosis of ovarian cancer (OC) TOV-21G cells through Wnt/β -catenin pathway and its mechanism. Methods: The cancer and para-cancerous tissue samples of 21 OC patients diagnosed in the Third Hospital of Wuhan from July 2022 to May 2023 were collected, and the SMS2 expression in the collected tissues was detected by immunohistochemistry. TOV-21G cells were cultured in vitro and grouped into control group, shRNA lentivirus negative control group (sh-NC group), SMS2 shRNA lentivirus group (sh-SMS2 group), Wnt/β-catenin pathway activator LiCl group (LiCl group), and sh-SMS2+LiCl group. Edu staining, Transwell method and flow cytometry were used to detect the proliferation, migration, invasion, and apoptosis of cells in each group. WB assay was used to detect the expression of SMS2, Ki67, cyclin D1, BAX, c-caspase3, Bcl-2 and Wnt/β -catenin pathway-related proteins (β -catenin, c-Myc, MMP-9) in the cells of each group. A TOV-21G cell transplanted tumor model was established in nude mice to observe the effects of SMS2 knockdown on the growth of transplanted tumors and the expression of SMS2 and β-catenin. Results: Compared with the para-cancerous tissues, the expression of SMS2 in OC tissues was increased obviously (P<0.05). After transfection with sh-SMS2, the expression level of SMS2 in TOV-21G cells was decreased obviously (P<0.05), the proliferation, migration, and invasion abilities of TOV-21G cells as well as the protein expression of Bcl-2, β-catenin, c-Myc, and MMP-9 were decreased obviously (all P<0.05), and the cell apoptosis rate, the protein expression of BAX and c-caspase3 were obviously increased (all P<0.05). LiCl could reverse the inhibitory effects of SMS2 knockdown on the proliferation, migration, invasion, and Wnt/β -catenin pathway of TOV-21G cells (all P<0.05). In vivo tumor formation experiments showed that SMS2 knockdown inhibited tumor growth and the expression of SMS2 and β-catenin (all P<0.05). Conclusion: SMS2 knockdown inhibits the proliferation, migration and invasion and promotes apoptosis of OC TOV-21G cells through Wnt/β-catenin signaling pathway, while LiCl treatment can reverse the inhibitory effects of SMS2 knockdown on the proliferation, migration and invasion of TOV-21G cells.
Objective: To investigate whether sphingomyelin synthase 2 (SMS2) regulates the proliferation, migration, invasion and apoptosis of ovarian cancer (OC) TOV-21G cells through Wnt/β -catenin pathway and its mechanism. Methods: The cancer and para-cancerous tissue samples of 21 OC patients diagnosed in the Third Hospital of Wuhan from July 2022 to May 2023 were collected, and the SMS2 expression in the collected tissues was detected by immunohistochemistry. TOV-21G cells were cultured in vitro and grouped into control group, shRNA lentivirus negative control group (sh-NC group), SMS2 shRNA lentivirus group (sh-SMS2 group), Wnt/β-catenin pathway activator LiCl group (LiCl group), and sh-SMS2+LiCl group. Edu staining, Transwell method and flow cytometry were used to detect the proliferation, migration, invasion, and apoptosis of cells in each group. WB assay was used to detect the expression of SMS2, Ki67, cyclin D1, BAX, c-caspase3, Bcl-2 and Wnt/β -catenin pathway-related proteins (β -catenin, c-Myc, MMP-9) in the cells of each group. A TOV-21G cell transplanted tumor model was established in nude mice to observe the effects of SMS2 knockdown on the growth of transplanted tumors and the expression of SMS2 and β-catenin. Results: Compared with the para-cancerous tissues, the expression of SMS2 in OC tissues was increased obviously (P<0.05). After transfection with sh-SMS2, the expression level of SMS2 in TOV-21G cells was decreased obviously (P<0.05), the proliferation, migration, and invasion abilities of TOV-21G cells as well as the protein expression of Bcl-2, β-catenin, c-Myc, and MMP-9 were decreased obviously (all P<0.05), and the cell apoptosis rate, the protein expression of BAX and c-caspase3 were obviously increased (all P<0.05). LiCl could reverse the inhibitory effects of SMS2 knockdown on the proliferation, migration, invasion, and Wnt/β -catenin pathway of TOV-21G cells (all P<0.05). In vivo tumor formation experiments showed that SMS2 knockdown inhibited tumor growth and the expression of SMS2 and β-catenin (all P<0.05). Conclusion: SMS2 knockdown inhibits the proliferation, migration and invasion and promotes apoptosis of OC TOV-21G cells through Wnt/β-catenin signaling pathway, while LiCl treatment can reverse the inhibitory effects of SMS2 knockdown on the proliferation, migration and invasion of TOV-21G cells.
2024, 31(1):40-46.
DOI: 10.3872/j.issn.1007-385X.2024.01.006
Abstract:
Objective: To investigate the expression of mucin 13 (MUC13) in lung adenocarcinoma tissues and its effects on the proliferation, apoptosis, migration, invasion, and epithelial-mesenchymal transition (EMT) of A549 cells as well as the possible mechanism. Methods: The differential expression of MUC13 in lung adenocarcinoma tissues, normal lung tissues, and para-cancerous tissues was analyzed using The Cancer Genome Atlas (TCGA) and high throughput Gene Expression Omnibus (GEO) databases. The mRNA and protein expression levels of MUC13 in human lung adenocarcinoma cells (NCI-H1395, NCI-H1975, H1299 and A549) and normal lung epithelial BEAS-2B cells were detected using qPCR and WB methods. siRNA technology was used to knock down MUC13 expression in A549 cells, and the experimental cells were divided into si-MUC13 group, NC group and si-MUC13+IGF-1 group. The effects of MUC13 knockdown on the proliferation, cell cycle, apoptosis, migration and invasion of A549 cells were detected by clony formation assay, flow cytometry and Transwell assay, respectively. WB assay was used to detect the effect of MUC13 knockdown on the protein expression of E-cadherin, N-cadherin, vimentin, EGFR, p-EGFR, PI3K, p-PI3K, AKT and p-AKT in A549 cells. Results: MUC13 was highly expressed in lung adenocarcinoma tissues and cells at both mRNA and protein levels (all P<0.01),and A549 cells with higher MUC13 expression were selected for subsequent experiments. After knocking down MUC13, the proliferation ability of A549 cells was significantly weakened, the number of cells in G0/G1 phase was significantly increased while the number of cells in G2/M phase and S phase was significantly decreased, the apoptosis rate was significantly increased, and the cell migration and invasion abilities were significantly weakened (all P<0.01); Moreover, the protein expression of E-cadherin in A549 cells was upregulated, while the protein expression of N-cadherin and vimentin was downregulated, and the ratios of p-EGFR/EGFR, p-PI3K/PI3K, and p-AKT/AKT were all reduced (all P<0.01). However, after adding pathway activator IGF-1, the p-EGFR/EGFR, p-PI3K/PI3K, and p-AKT/AKT ratios in A549 cells all increased (all P<0.01). Conclusion: MUC13 is highly expressed in lung adenocarcinoma tissues and cells, and it promotes cell proliferation, migration, invasion and EMT of A549 cells, possibly through the activation of the EGFR/PI3K/AKT signaling pathway.
Objective: To investigate the expression of mucin 13 (MUC13) in lung adenocarcinoma tissues and its effects on the proliferation, apoptosis, migration, invasion, and epithelial-mesenchymal transition (EMT) of A549 cells as well as the possible mechanism. Methods: The differential expression of MUC13 in lung adenocarcinoma tissues, normal lung tissues, and para-cancerous tissues was analyzed using The Cancer Genome Atlas (TCGA) and high throughput Gene Expression Omnibus (GEO) databases. The mRNA and protein expression levels of MUC13 in human lung adenocarcinoma cells (NCI-H1395, NCI-H1975, H1299 and A549) and normal lung epithelial BEAS-2B cells were detected using qPCR and WB methods. siRNA technology was used to knock down MUC13 expression in A549 cells, and the experimental cells were divided into si-MUC13 group, NC group and si-MUC13+IGF-1 group. The effects of MUC13 knockdown on the proliferation, cell cycle, apoptosis, migration and invasion of A549 cells were detected by clony formation assay, flow cytometry and Transwell assay, respectively. WB assay was used to detect the effect of MUC13 knockdown on the protein expression of E-cadherin, N-cadherin, vimentin, EGFR, p-EGFR, PI3K, p-PI3K, AKT and p-AKT in A549 cells. Results: MUC13 was highly expressed in lung adenocarcinoma tissues and cells at both mRNA and protein levels (all P<0.01),and A549 cells with higher MUC13 expression were selected for subsequent experiments. After knocking down MUC13, the proliferation ability of A549 cells was significantly weakened, the number of cells in G0/G1 phase was significantly increased while the number of cells in G2/M phase and S phase was significantly decreased, the apoptosis rate was significantly increased, and the cell migration and invasion abilities were significantly weakened (all P<0.01); Moreover, the protein expression of E-cadherin in A549 cells was upregulated, while the protein expression of N-cadherin and vimentin was downregulated, and the ratios of p-EGFR/EGFR, p-PI3K/PI3K, and p-AKT/AKT were all reduced (all P<0.01). However, after adding pathway activator IGF-1, the p-EGFR/EGFR, p-PI3K/PI3K, and p-AKT/AKT ratios in A549 cells all increased (all P<0.01). Conclusion: MUC13 is highly expressed in lung adenocarcinoma tissues and cells, and it promotes cell proliferation, migration, invasion and EMT of A549 cells, possibly through the activation of the EGFR/PI3K/AKT signaling pathway.
2024, 31(1):47-53.
DOI: 10.3872/j.issn.1007-385X.2024.01.007
Abstract:
Objective: To explore the relationship between the expression level of mannose-binding lectin 2 (LMAN2) in hormone receptor (HR)-positive breast cancer tissues and patient prognosis as well as its effects on the proliferation and migration of MCF-7 cells. Methods: The differential expression of LMAN2 in breast cancer tissues and normal breast tissues as well as its relationship with patients' prognosis were analyzed by TCGA, Bc-GenExMiner, GEPIA and Kaplan-Meier Plotter databases. si-LMAN2#1, si-LMAN2#2 and si-NC were transfected into MCF-7 cells using small RNA interference technology, and the LMAN overexpression vector (pc-LMAN) and empty vector pcDNA3.1 negative control (pc-NC) were transfected into MCF-7 cells; and accordingly, the experimental groups were named si-LMAN2#1 group, si-LMAN2#2 group, si-NC group, pc-LMAN2 group and pc-NC group. The mRNA and protein expression levels of LMAN2 in MCF-7 cells of each group were detected by qPCR and WB assay, respectively. The effects of knockdown and overexpression of the LMAN2 on the proliferation, colony formation and migration as well as the expression of AKT signaling pathway-related proteins in MCF-7 cells were detected using CCK-8, colony formation, Transwell migration and WB assay, etc. Results: The expression level of LMAN2 in breast cancer tissues was significantly higher than that in normal breast tissues (P<0.001), and the expression of LMAN2 in HR-positive breast cancer tissues was significantly higher than that in HR-negative breast cancer tissues (P<0.001). In contrast to low LMAN2 expression, high expression of LMAN2 was associated with poor prognosis in HR-positive breast cancer patients. Knockdown of LMAN2 significantly inhibited the proliferation and migration abilities of MCF-7 cells (P<0.01 or P<0.001), while overexpression of LMAN2 significantly enhanced the proliferation and migration abilities of MCF-7 cells (all P<0.001). The protein expression levels of PTEN and P21 in MCF-7 cells with LMAN2 knockdown were significantly elevated, while the protein expression of p-AKT was significantly decreased (all P<0.01). Conclusion: LMAN2 is highly expressed in breast cancer tissues and HR-positive breast cancer tissues and is associated with poor prognosis. The high expression of LMAN2 is associated with the proliferation and migration of MCF-7 cells, and the mechanism may involve the AKT signaling pathway.
Objective: To explore the relationship between the expression level of mannose-binding lectin 2 (LMAN2) in hormone receptor (HR)-positive breast cancer tissues and patient prognosis as well as its effects on the proliferation and migration of MCF-7 cells. Methods: The differential expression of LMAN2 in breast cancer tissues and normal breast tissues as well as its relationship with patients' prognosis were analyzed by TCGA, Bc-GenExMiner, GEPIA and Kaplan-Meier Plotter databases. si-LMAN2#1, si-LMAN2#2 and si-NC were transfected into MCF-7 cells using small RNA interference technology, and the LMAN overexpression vector (pc-LMAN) and empty vector pcDNA3.1 negative control (pc-NC) were transfected into MCF-7 cells; and accordingly, the experimental groups were named si-LMAN2#1 group, si-LMAN2#2 group, si-NC group, pc-LMAN2 group and pc-NC group. The mRNA and protein expression levels of LMAN2 in MCF-7 cells of each group were detected by qPCR and WB assay, respectively. The effects of knockdown and overexpression of the LMAN2 on the proliferation, colony formation and migration as well as the expression of AKT signaling pathway-related proteins in MCF-7 cells were detected using CCK-8, colony formation, Transwell migration and WB assay, etc. Results: The expression level of LMAN2 in breast cancer tissues was significantly higher than that in normal breast tissues (P<0.001), and the expression of LMAN2 in HR-positive breast cancer tissues was significantly higher than that in HR-negative breast cancer tissues (P<0.001). In contrast to low LMAN2 expression, high expression of LMAN2 was associated with poor prognosis in HR-positive breast cancer patients. Knockdown of LMAN2 significantly inhibited the proliferation and migration abilities of MCF-7 cells (P<0.01 or P<0.001), while overexpression of LMAN2 significantly enhanced the proliferation and migration abilities of MCF-7 cells (all P<0.001). The protein expression levels of PTEN and P21 in MCF-7 cells with LMAN2 knockdown were significantly elevated, while the protein expression of p-AKT was significantly decreased (all P<0.01). Conclusion: LMAN2 is highly expressed in breast cancer tissues and HR-positive breast cancer tissues and is associated with poor prognosis. The high expression of LMAN2 is associated with the proliferation and migration of MCF-7 cells, and the mechanism may involve the AKT signaling pathway.
CHEN Xiang
,
IALENG·Rehatihan
,
GU Guomin
,
ABUDILI·Abuduxuku
,
SHABINA·Dilixiati
,
YANG Zhe
,
WANG Haifeng
2024, 31(1):54-61.
DOI: 10.3872/j.issn.1007-385X.2024.01.008
Abstract:
Objective: To investigate the relationship between the incidence of immune checkpoint inhibitor-associated pneumonia (CIP) and the efficacy of immunotherapy in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs), and to explore the prognostic factors of patients receiving ICI treatment. Methods: The clinical and follow-up data of 145 NSCLC patients treated with ICIs in the Affiliated Cancer Hospital of Xinjiang Medical University from March 2020 to March 2023 were retrospectively analyzed. The patients were divided into CIP group and non-CIP group. The patients with CIP were sub-divided into mild (grade 1, 2) and severe (grade 3, 4) CIP subgroups. The effects of the occurrence and severity of CIP on the overall survival (OS) time and progression-free survival (PFS) time of the patients were analyzed by comparing the survival curve using Kaplan-Meier method. Univariate and multivariate COX proportional hazard regression models were used to analyze the prognostic factors associated with PFS and OS. Results: A total of 26 patients developed CIP, with an incidence rate of 17.93% (26/145), and the incidence of severe CIP was 3.4%. The PFS in CIP group was significantly longer than that in non-CIP group (12.3 vs 7.6 months, P<0.05). There was no significant difference in OS between CIP group and non-CIP group (16.2 vs 15.8 months, P>0.05). Subgroup analysis showed that there were no significant differences in PFS (12.2 vs 12.9 months) and OS (16.1 vs 17.8 months) between mild CIP and severe CIP groups (all P>0.05). Multivariate COX regression analysis showed that CIP (HR=0.55, 95%CI [0.33,0.90], P=0.02) and the course of immunotherapy >6 cycles (HR=0.51, 95%CI [0.31, 0.85], P=0.01) were favorable prognostic factors for PFS. The course of immunotherapy >6 cycles (HR=0.4, 95%CI [0.18,0.88], P=0.02) was a favorable prognostic factor for OS. Conclusion: The incidence of CIP is 17.93%. The occurrence of CIP is closely related to the prolongation of PFS. Immunotherapy course >6 cycles is a favorable prognostic factor for PFS and OS of NSCLC patients.
Objective: To investigate the relationship between the incidence of immune checkpoint inhibitor-associated pneumonia (CIP) and the efficacy of immunotherapy in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs), and to explore the prognostic factors of patients receiving ICI treatment. Methods: The clinical and follow-up data of 145 NSCLC patients treated with ICIs in the Affiliated Cancer Hospital of Xinjiang Medical University from March 2020 to March 2023 were retrospectively analyzed. The patients were divided into CIP group and non-CIP group. The patients with CIP were sub-divided into mild (grade 1, 2) and severe (grade 3, 4) CIP subgroups. The effects of the occurrence and severity of CIP on the overall survival (OS) time and progression-free survival (PFS) time of the patients were analyzed by comparing the survival curve using Kaplan-Meier method. Univariate and multivariate COX proportional hazard regression models were used to analyze the prognostic factors associated with PFS and OS. Results: A total of 26 patients developed CIP, with an incidence rate of 17.93% (26/145), and the incidence of severe CIP was 3.4%. The PFS in CIP group was significantly longer than that in non-CIP group (12.3 vs 7.6 months, P<0.05). There was no significant difference in OS between CIP group and non-CIP group (16.2 vs 15.8 months, P>0.05). Subgroup analysis showed that there were no significant differences in PFS (12.2 vs 12.9 months) and OS (16.1 vs 17.8 months) between mild CIP and severe CIP groups (all P>0.05). Multivariate COX regression analysis showed that CIP (HR=0.55, 95%CI [0.33,0.90], P=0.02) and the course of immunotherapy >6 cycles (HR=0.51, 95%CI [0.31, 0.85], P=0.01) were favorable prognostic factors for PFS. The course of immunotherapy >6 cycles (HR=0.4, 95%CI [0.18,0.88], P=0.02) was a favorable prognostic factor for OS. Conclusion: The incidence of CIP is 17.93%. The occurrence of CIP is closely related to the prolongation of PFS. Immunotherapy course >6 cycles is a favorable prognostic factor for PFS and OS of NSCLC patients.
2024, 31(1):62-74.
DOI: 10.3872/j.issn.1007-385X.2024.01.009
Abstract:
Objective: To explore the immunotherapy-related oxidative stress genes (IROSGs) in lung adenocarcinoma (LUAD) and their relationship with immune infiltration and patient prognosis. Methods: The expression profile IROSG and corresponding clinical information of LUAD patients were downloaded from the TCGA and GEO databases. To identify immunotherapy-related genes, differential gene expression analysis was conducted on a cohort of non-small cell lung cancer (NSCLC) patients undergoing immunotherapy. By intersecting the results with oxidative stress-related genes screened from the GeneCards database, the IROSG set was obtained. The LUAD patients were clustered based on the obtained IROSG, and a prognostic model was constructed by performing univariate COX regression analysis, Lasso and multivariate COX regression analysis on the differentially expressed genes of the subtypes. The risk score was calculated for each patient based on the model, and patients were categorized into high-risk and low-risk groups. The predictive efficacy of the model was validated using multiple external validation sets, and further analyses were performed including tumor microenvironment (TME) analysis, drug sensitivity analysis, and prediction of immunotherapy response. Results: A total of 82 IROSGs were obtained through comprehensive database analysis, and LUAD patients with high IROSG expression had a better prognosis (P<0.05). The prognostic model for LUAD patients constructed on the basis of expression of IROSG and risk scores showed good predictive performance. A nomogram was constructed based on the prognostic factors such as risk score and patient characteristics, and its calibration curve demonstrated good performance to predict the overall survival rate in LUAD patients. The low-risk group was primarily enriched in pathways such as allograft rejection and autoimmune diseases, while the high-risk group was primarily enriched in pathways such as cell cycle and DNA replication. Additionally, the levels of immune cell infiltration were higher in the LUAD tissues of low-risk group. Combining high- and low-risk scores with tumor mutation burden (TMB), TME, tumor immune dysfunction and exclusion (TIDE) scores, as well as immune checkpoint molecule expression levels, can effectively predict the prognosis of LUAD patients, immune therapy response, and sensitivity to chemotherapy drugs. Conclusion: In this study, we developed a model for predicting the prognosis and immunotherapy response of LUAD patients, providing a theoretical basis for personalized treatment of LUAD patients.
Objective: To explore the immunotherapy-related oxidative stress genes (IROSGs) in lung adenocarcinoma (LUAD) and their relationship with immune infiltration and patient prognosis. Methods: The expression profile IROSG and corresponding clinical information of LUAD patients were downloaded from the TCGA and GEO databases. To identify immunotherapy-related genes, differential gene expression analysis was conducted on a cohort of non-small cell lung cancer (NSCLC) patients undergoing immunotherapy. By intersecting the results with oxidative stress-related genes screened from the GeneCards database, the IROSG set was obtained. The LUAD patients were clustered based on the obtained IROSG, and a prognostic model was constructed by performing univariate COX regression analysis, Lasso and multivariate COX regression analysis on the differentially expressed genes of the subtypes. The risk score was calculated for each patient based on the model, and patients were categorized into high-risk and low-risk groups. The predictive efficacy of the model was validated using multiple external validation sets, and further analyses were performed including tumor microenvironment (TME) analysis, drug sensitivity analysis, and prediction of immunotherapy response. Results: A total of 82 IROSGs were obtained through comprehensive database analysis, and LUAD patients with high IROSG expression had a better prognosis (P<0.05). The prognostic model for LUAD patients constructed on the basis of expression of IROSG and risk scores showed good predictive performance. A nomogram was constructed based on the prognostic factors such as risk score and patient characteristics, and its calibration curve demonstrated good performance to predict the overall survival rate in LUAD patients. The low-risk group was primarily enriched in pathways such as allograft rejection and autoimmune diseases, while the high-risk group was primarily enriched in pathways such as cell cycle and DNA replication. Additionally, the levels of immune cell infiltration were higher in the LUAD tissues of low-risk group. Combining high- and low-risk scores with tumor mutation burden (TMB), TME, tumor immune dysfunction and exclusion (TIDE) scores, as well as immune checkpoint molecule expression levels, can effectively predict the prognosis of LUAD patients, immune therapy response, and sensitivity to chemotherapy drugs. Conclusion: In this study, we developed a model for predicting the prognosis and immunotherapy response of LUAD patients, providing a theoretical basis for personalized treatment of LUAD patients.
2024, 31(1):75-81.
DOI: 10.3872/j.issn.1007-385X.2024.01.010
Abstract:
肝细胞癌（HCC）是转移性极高、预后极差的恶性肿瘤之一，寻找与其发生与发展密切相关的预后标志物和治疗靶点是提高HCC预后监测和治疗的关键。驱动蛋白超家族（KIF）在HCC组织中特异性高表达，并且这种异常表达可通过激活上皮间质转化（EMT）促进HCC转移，影响HCC的预后和药物治疗的疗效，提示KIF 可能是HCC预后监测和治疗中极具前景的预后标志物和分子治疗靶点。阐明KIF 在HCC转移、预后和治疗中的作用及其机制，以及其作为HCC预后标志物和分子治疗靶点的临床意义，对开发HCC的预后监测及靶向治疗新策略至关重要。
肝细胞癌（HCC）是转移性极高、预后极差的恶性肿瘤之一，寻找与其发生与发展密切相关的预后标志物和治疗靶点是提高HCC预后监测和治疗的关键。驱动蛋白超家族（KIF）在HCC组织中特异性高表达，并且这种异常表达可通过激活上皮间质转化（EMT）促进HCC转移，影响HCC的预后和药物治疗的疗效，提示KIF 可能是HCC预后监测和治疗中极具前景的预后标志物和分子治疗靶点。阐明KIF 在HCC转移、预后和治疗中的作用及其机制，以及其作为HCC预后标志物和分子治疗靶点的临床意义，对开发HCC的预后监测及靶向治疗新策略至关重要。
2024, 31(1):82-88.
DOI: 10.3872/j.issn.1007-385X.2024.01.011
Abstract:
膜联蛋白A2（ANXA2）属于膜联蛋白家族成员之一，参与调控正常细胞膜运输、细胞骨架构成和细胞增殖等生物学功能。近年来的研究发现，ANXA2可以促进恶性肿瘤细胞增殖、侵袭和迁移及黏附，并且影响肿瘤治疗抵抗和免疫逃逸，ANXA2在肿瘤组织中的表达水平与患者预后密切相关，有望成为预后评估的标志物。此外，已有研究在裸鼠皮下异种移植神经母细胞瘤模型中尝试靶向ANXA2基因治疗，并有效增强了肿瘤化疗药物的敏感性。尽管前期进行了大量的相关研究，但到目前为止对于ANXA2如何介导肿瘤发生、发展的具体机制仍然缺乏系统性研究。深入了解近年来ANXA2在调控肿瘤细胞上皮间质转化、细胞骨架动力学、增殖周期、代谢和免疫学等方面的研究进展，对肿瘤治疗靶点及预后标志物的研发具有重要意义。
膜联蛋白A2（ANXA2）属于膜联蛋白家族成员之一，参与调控正常细胞膜运输、细胞骨架构成和细胞增殖等生物学功能。近年来的研究发现，ANXA2可以促进恶性肿瘤细胞增殖、侵袭和迁移及黏附，并且影响肿瘤治疗抵抗和免疫逃逸，ANXA2在肿瘤组织中的表达水平与患者预后密切相关，有望成为预后评估的标志物。此外，已有研究在裸鼠皮下异种移植神经母细胞瘤模型中尝试靶向ANXA2基因治疗，并有效增强了肿瘤化疗药物的敏感性。尽管前期进行了大量的相关研究，但到目前为止对于ANXA2如何介导肿瘤发生、发展的具体机制仍然缺乏系统性研究。深入了解近年来ANXA2在调控肿瘤细胞上皮间质转化、细胞骨架动力学、增殖周期、代谢和免疫学等方面的研究进展，对肿瘤治疗靶点及预后标志物的研发具有重要意义。
2024, 31(1):89-93.
DOI: 10.3872/j.issn.1007-385X.2024.01.012
Abstract:
鉴于免疫检查点抑制剂（ICI）在非小细胞肺癌及黑色素瘤治疗方面取得的令人瞩目的成效，其关于不同瘤种及不同联合方案的临床试验也随之展开。随着ICI 的大规模应用，其引发的自身免疫毒性即免疫相关不良反应（irAE）受到了广泛关注。 irAE 可能会导致治疗的终止甚至危及生命，早期识别和处理至关重要，然而其发生的具体机制尚不明确，因此亟需寻找高效、特异的irAE 预测因素。目前，人口学特征及病理学特征（性别、年龄、自身免疫病史和用药史等），免疫细胞（血细胞计数、嗜酸性粒细胞、T细胞和B细胞水平等），细胞因子，自身抗体，肠道微生物和全身免疫炎症指数等用于预测irAE 发生的价值已被关注并开展研究，本文综述了相关研究进展，为确定irAE的预测因素提供了参考。
鉴于免疫检查点抑制剂（ICI）在非小细胞肺癌及黑色素瘤治疗方面取得的令人瞩目的成效，其关于不同瘤种及不同联合方案的临床试验也随之展开。随着ICI 的大规模应用，其引发的自身免疫毒性即免疫相关不良反应（irAE）受到了广泛关注。 irAE 可能会导致治疗的终止甚至危及生命，早期识别和处理至关重要，然而其发生的具体机制尚不明确，因此亟需寻找高效、特异的irAE 预测因素。目前，人口学特征及病理学特征（性别、年龄、自身免疫病史和用药史等），免疫细胞（血细胞计数、嗜酸性粒细胞、T细胞和B细胞水平等），细胞因子，自身抗体，肠道微生物和全身免疫炎症指数等用于预测irAE 发生的价值已被关注并开展研究，本文综述了相关研究进展，为确定irAE的预测因素提供了参考。
2024, 31(1):94-100.
DOI: 10.3872/j.issn.1007-385X.2024.01.013
Abstract:
随着乳腺癌患者生存期的延长，肿瘤耐药性成为治疗过程的严峻挑战之一，临床通常将细胞死亡标志物的增加作为预测乳腺肿瘤患者生存率提高的标准。通过刺激肿瘤细胞死亡途径来提高抗肿瘤药物治疗的效果，使用某些佐剂是一种可行的方法。研究表明，二甲双胍（Met）是治疗Ⅱ型糖尿病的一线药物，同时具有抗肿瘤特性，其能增强细胞死亡机制，尤其是促进肿瘤细胞自噬、凋亡和铁死亡。同时证明，Met 对免疫系统的刺激作用在诱导肿瘤细胞死亡方面发挥作用，其诱导不同细胞死亡机制在增敏抗肿瘤药物治疗中起着关键作用。本文论述了Met 对乳腺癌肿瘤微环境（TME）的调控作用机制及其在抗肿瘤药物治疗中的增敏作用，对Met在临床前和临床免疫治疗中的研究方向提出建议。
随着乳腺癌患者生存期的延长，肿瘤耐药性成为治疗过程的严峻挑战之一，临床通常将细胞死亡标志物的增加作为预测乳腺肿瘤患者生存率提高的标准。通过刺激肿瘤细胞死亡途径来提高抗肿瘤药物治疗的效果，使用某些佐剂是一种可行的方法。研究表明，二甲双胍（Met）是治疗Ⅱ型糖尿病的一线药物，同时具有抗肿瘤特性，其能增强细胞死亡机制，尤其是促进肿瘤细胞自噬、凋亡和铁死亡。同时证明，Met 对免疫系统的刺激作用在诱导肿瘤细胞死亡方面发挥作用，其诱导不同细胞死亡机制在增敏抗肿瘤药物治疗中起着关键作用。本文论述了Met 对乳腺癌肿瘤微环境（TME）的调控作用机制及其在抗肿瘤药物治疗中的增敏作用，对Met在临床前和临床免疫治疗中的研究方向提出建议。
2024, 31(1):101-104.
DOI: 10.3872/j.issn.1007-385X.2024.01.014
Abstract:
乳腺癌肝转移发生率较高，一旦发生将严重影响患者预后，肝转移患者可无明显阳性体征，其化疗效果差，缺乏有效的治疗手段。患者女性，70岁，经左乳腺癌改良根治术辅助放化疗结合内分泌治疗后3年发现肝转移，继采用多种化疗及内分泌治疗方案，期间出现Ⅱ度神经毒性和Ⅲ度骨髓抑制，患者无法耐受，且肝转移灶不断增大。2023 年3月入本院行肝动脉介入化疗术联合内分泌治疗，同时予以中药汤剂香贝散加减口服治疗，治疗4周期后，复查CT提示肝转移灶缩小近75%，疗效评价为部分缓解，患者的生活质量明显提高。该例中西医结合的治疗模式为难治性乳腺癌肝转移及其他难治性恶性肿瘤患者的治疗提供了新思路和新方法。
乳腺癌肝转移发生率较高，一旦发生将严重影响患者预后，肝转移患者可无明显阳性体征，其化疗效果差，缺乏有效的治疗手段。患者女性，70岁，经左乳腺癌改良根治术辅助放化疗结合内分泌治疗后3年发现肝转移，继采用多种化疗及内分泌治疗方案，期间出现Ⅱ度神经毒性和Ⅲ度骨髓抑制，患者无法耐受，且肝转移灶不断增大。2023 年3月入本院行肝动脉介入化疗术联合内分泌治疗，同时予以中药汤剂香贝散加减口服治疗，治疗4周期后，复查CT提示肝转移灶缩小近75%，疗效评价为部分缓解，患者的生活质量明显提高。该例中西医结合的治疗模式为难治性乳腺癌肝转移及其他难治性恶性肿瘤患者的治疗提供了新思路和新方法。
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- 主办单位：Chinese Society of Immunology, Chinese Anti-cancer Association
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- 刊号：ISSN 1007-385X
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.
Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.