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Volume 29,Issue 1,2022 Table of Contents
2022, 29(1):1-10.
DOI: 10.3872/j.issn.1007-385X.2022.01.001
Abstract:
Personalized neoantigen cancer vaccines have gradually emerged, with breakthroughs being made in the treatment of cancers such as melanoma, lung cancer and glioma, demonstrating potential and promising prospects. With the decrease in sequencing costs, continuous breakthroughs in artificial intelligence (AI) technology and the deepened understanding of tumor immunotherapy, it is feasible to conduct dynamic whole-process monitoring and to capture the clone diversity of tumor-related somatic mutations in tumor patients, along with which the developed neoantigen cancer vaccines have become the current research hotspot with promising future. This review systematically summarizes the research context and progress as well as looks into the future key development of the personalized neoantigen cancer vaccines, an emerging precise immunotherapy, from the aspects of screening and validation of neoantigens, clinical application, challenges, and future trends.
Personalized neoantigen cancer vaccines have gradually emerged, with breakthroughs being made in the treatment of cancers such as melanoma, lung cancer and glioma, demonstrating potential and promising prospects. With the decrease in sequencing costs, continuous breakthroughs in artificial intelligence (AI) technology and the deepened understanding of tumor immunotherapy, it is feasible to conduct dynamic whole-process monitoring and to capture the clone diversity of tumor-related somatic mutations in tumor patients, along with which the developed neoantigen cancer vaccines have become the current research hotspot with promising future. This review systematically summarizes the research context and progress as well as looks into the future key development of the personalized neoantigen cancer vaccines, an emerging precise immunotherapy, from the aspects of screening and validation of neoantigens, clinical application, challenges, and future trends.
2022, 29(1):11-17.
DOI: 10.3872/j.issn.1007-385X.2022.01.002
Abstract:
Objective:To investigate whether targeted inhibition of CD38 by shRNA can enhance the anticancer function of anti-CD38 CAR T cells. Methods: The anti-CD38 CAR molecules with targeted inhibition of CD38 by shRNA were constructed. After being successfully packaged with retroviral vector, the CAR molecules were transferred into human primary T cells to prepare CAR-T cells,which were then divided into shRNA1-CD38 CAR-T group, shRNA2-CD38 CAR-T group and control group (shR-NC-CD38 CAR-T cells). The relative expression of CD38 mRNA in CAR-T cells was detected by qPCR method, and the proliferation index of CAR-T cells cultured ex vivo for 0-14 days was calculated. The proliferation of CAR-T cells co-cultured with human Burkitt lymphoma Raji-luc cells or human multiple myeloma peripheral blood B lymphocytes RPMI-8226-luc was detected by CFSE method. The killing efficiency of CAR-T cells against Raji-luc and RPMI-8226-luc cells at different effector-target ratios (1∶1, 1∶2, 1∶4, 1∶8) was detected by luciferase chemiluminescence. The level of IFN- γ in the supernatant of CAR-T cells co-cultured with Raji-luc cells or RPMI-8226-luc cells was detected by ELISA. The expression of PD-1, one of the T cell exhaustion biomarkers, on the surface of CAR-T cells was detected by flow cytometry. Results: The titers of shR-NC-CD38 CAR, shRNA1-CD38 CAR and shRNA2-CD38 CAR retroviral vectors were all about 1×107 copies/mL. The transduction efficiency (CAR positive rate) in cells of shR-NC-CD38 CAR-T group, shRNA1-CD38 CAR-T group and shRNA2-CD38 CAR-T group was 60.3%, 67.0% and 57.4%, respectively. Compared with the control group, the expression level of CD38 mRNA in shRNA2-CD38 CAR-T group was significantly lower (P<0.01),indicating the successful construction of shRNA-CD38 CAR-T cells. For the cells in shRNA2-CD38 CAR-T group, their ex vivo proliferation ability was stronger, the killing efficiency against two CD38 positive tumor cells was higher, the release level of IFN-γ was higher, and the surface expression level of PD-1 was lower, as compared with the other two groups (P<0.05). Conclusion: A novel anti[1]CD38 CAR-T cells with targeted inhibition of CD38 by shRNA was successfully constructed, which exhibited obvious advantages in antitumor function.
Objective:To investigate whether targeted inhibition of CD38 by shRNA can enhance the anticancer function of anti-CD38 CAR T cells. Methods: The anti-CD38 CAR molecules with targeted inhibition of CD38 by shRNA were constructed. After being successfully packaged with retroviral vector, the CAR molecules were transferred into human primary T cells to prepare CAR-T cells,which were then divided into shRNA1-CD38 CAR-T group, shRNA2-CD38 CAR-T group and control group (shR-NC-CD38 CAR-T cells). The relative expression of CD38 mRNA in CAR-T cells was detected by qPCR method, and the proliferation index of CAR-T cells cultured ex vivo for 0-14 days was calculated. The proliferation of CAR-T cells co-cultured with human Burkitt lymphoma Raji-luc cells or human multiple myeloma peripheral blood B lymphocytes RPMI-8226-luc was detected by CFSE method. The killing efficiency of CAR-T cells against Raji-luc and RPMI-8226-luc cells at different effector-target ratios (1∶1, 1∶2, 1∶4, 1∶8) was detected by luciferase chemiluminescence. The level of IFN- γ in the supernatant of CAR-T cells co-cultured with Raji-luc cells or RPMI-8226-luc cells was detected by ELISA. The expression of PD-1, one of the T cell exhaustion biomarkers, on the surface of CAR-T cells was detected by flow cytometry. Results: The titers of shR-NC-CD38 CAR, shRNA1-CD38 CAR and shRNA2-CD38 CAR retroviral vectors were all about 1×107 copies/mL. The transduction efficiency (CAR positive rate) in cells of shR-NC-CD38 CAR-T group, shRNA1-CD38 CAR-T group and shRNA2-CD38 CAR-T group was 60.3%, 67.0% and 57.4%, respectively. Compared with the control group, the expression level of CD38 mRNA in shRNA2-CD38 CAR-T group was significantly lower (P<0.01),indicating the successful construction of shRNA-CD38 CAR-T cells. For the cells in shRNA2-CD38 CAR-T group, their ex vivo proliferation ability was stronger, the killing efficiency against two CD38 positive tumor cells was higher, the release level of IFN-γ was higher, and the surface expression level of PD-1 was lower, as compared with the other two groups (P<0.05). Conclusion: A novel anti[1]CD38 CAR-T cells with targeted inhibition of CD38 by shRNA was successfully constructed, which exhibited obvious advantages in antitumor function.
2022, 29(1):18-22.
DOI: 10.3872/j.issn.1007-385X.2022.01.003
Abstract:
Objective: To investigate the effect of mixed lineage leukemia 5 (MLL5) gene on growth of colon cancer CT26 cell transplanted tumors in mice and its molecular mechanism. Methods: The colon cancer CT26 cell model with MLL5 gene deletion or double deletion of MLL5 and DDX58 (encoding RIG-1 gene) was constructed using CRISPR/Cas9 technology, and the knock-out efficiency was verified using Sanger sequencing and WB. Then, the constructed CT26 cells were inoculated into the scapular subcutaneous tissues of wild BALB/c mice and immunodeficient mice (NSG) to establish the gene-deficient CT26 cell transplanted tumor model. The tumor growth and the overall survival (OS) of tumor-bearing mice were observed. Results: In wild BALB/c mice, MLL5 gene depletion significantly slowed the tumor growth down and prolonged the OS of mice as compared with the mice transplanted with CT26 cells with normal MIL5 expression (P
Objective: To investigate the effect of mixed lineage leukemia 5 (MLL5) gene on growth of colon cancer CT26 cell transplanted tumors in mice and its molecular mechanism. Methods: The colon cancer CT26 cell model with MLL5 gene deletion or double deletion of MLL5 and DDX58 (encoding RIG-1 gene) was constructed using CRISPR/Cas9 technology, and the knock-out efficiency was verified using Sanger sequencing and WB. Then, the constructed CT26 cells were inoculated into the scapular subcutaneous tissues of wild BALB/c mice and immunodeficient mice (NSG) to establish the gene-deficient CT26 cell transplanted tumor model. The tumor growth and the overall survival (OS) of tumor-bearing mice were observed. Results: In wild BALB/c mice, MLL5 gene depletion significantly slowed the tumor growth down and prolonged the OS of mice as compared with the mice transplanted with CT26 cells with normal MIL5 expression (P
GAO Shenshuo
,
ZHANG Zhikai
,
YIN Guoqing
,
ZHANG Hongxia
,
WANG Xubin
,
MA Yan
,
LIU Hongjun
,
LI Leping
,
GUO Xiaobo
2022, 29(1):23-29.
DOI: 10.3872/j.issn.1007-385X.2022.01.004
Abstract:
Objective: To investigate the effects of miR-875-5p on proliferation, migration and invasion of gastric cancer (GC) cells and its mechanism. Methods: The expression level of miR-875-5p was detected by qPCR in GC cell lines (BGC-823, HGC-27,MGC-803, SGC-7901, AGS, MKN-45) and gastric epithelial GES-1 cells. MiR-875-5p mimics/inhibitors or their negative control plasmids (miR-NC/anti-miR-NC) were transfected into AGS or MKN-45 cells by liposome transfection technique to construct miR-875-5p overexpression or knockdown cell model. Cells in blank control group (Control group) were not transfected. The effects of miR-875-5p on cell proliferation, clone formation, migration and invasion were detected by CCK-8 assay, colony formation assay and Transwell assay, respectively. The targeting relationship between miR-875-5p and upstream stimulatory factor 2 (USF2) was verified by dual-luciferase reporter gene assay. The regulation of miR-875-5p on USF2 as well as the expression of USF2 protein was confirmed by WB assay. After the construction of MKN-45 cell transplanted tumor model in nude mice, the effect of miR-875-5p overexpression on tumorigenesis of MKN-45 cells was detected. Results: The expression level of miR-875-5p in 6 GC cells was significantly lower than that in gastric epithelial GES-1 cells (all P<0.01). Compared with Control group and miR-NC group, the proliferation, clone formation rate, number of migrated and invaded cells, and USF2 protein expression level in AGS cells were significantly decreased in miR-875-5p mimic group (P<0.05 or P<0.01), while those were significantly increased in MKN-45 cells of miR-875-5p inhibitor group (P<0.05 or P<0.01). Dual-luciferase reporter gene assay demonstrated that miR-875-5p could directly target USF2 gene. In vivo tumorigenesis experiment results showed that overexpression of miR-875-5p significantly inhibited the growth of MKN-45 cell transplanted tumors (all P<0.01). Conclusion: miR-875-5p inhibits proliferation, migration and invasion of GC cells by targeting USF2.
Objective: To investigate the effects of miR-875-5p on proliferation, migration and invasion of gastric cancer (GC) cells and its mechanism. Methods: The expression level of miR-875-5p was detected by qPCR in GC cell lines (BGC-823, HGC-27,MGC-803, SGC-7901, AGS, MKN-45) and gastric epithelial GES-1 cells. MiR-875-5p mimics/inhibitors or their negative control plasmids (miR-NC/anti-miR-NC) were transfected into AGS or MKN-45 cells by liposome transfection technique to construct miR-875-5p overexpression or knockdown cell model. Cells in blank control group (Control group) were not transfected. The effects of miR-875-5p on cell proliferation, clone formation, migration and invasion were detected by CCK-8 assay, colony formation assay and Transwell assay, respectively. The targeting relationship between miR-875-5p and upstream stimulatory factor 2 (USF2) was verified by dual-luciferase reporter gene assay. The regulation of miR-875-5p on USF2 as well as the expression of USF2 protein was confirmed by WB assay. After the construction of MKN-45 cell transplanted tumor model in nude mice, the effect of miR-875-5p overexpression on tumorigenesis of MKN-45 cells was detected. Results: The expression level of miR-875-5p in 6 GC cells was significantly lower than that in gastric epithelial GES-1 cells (all P<0.01). Compared with Control group and miR-NC group, the proliferation, clone formation rate, number of migrated and invaded cells, and USF2 protein expression level in AGS cells were significantly decreased in miR-875-5p mimic group (P<0.05 or P<0.01), while those were significantly increased in MKN-45 cells of miR-875-5p inhibitor group (P<0.05 or P<0.01). Dual-luciferase reporter gene assay demonstrated that miR-875-5p could directly target USF2 gene. In vivo tumorigenesis experiment results showed that overexpression of miR-875-5p significantly inhibited the growth of MKN-45 cell transplanted tumors (all P<0.01). Conclusion: miR-875-5p inhibits proliferation, migration and invasion of GC cells by targeting USF2.
2022, 29(1):30-36.
DOI: 10.3872/j.issn.1007-385X.2022.01.005
Abstract:
Objective: To investigate the effect of miR-17-5p and SET domain containing 2 (SETD2) on proliferation and apoptosis of myelodysplastic syndrome (MDS) SKM-1 cells and its mechanism. Methods: Bone marrow samples of 35 MDS patients (MDS group) and 35 healthy persons (control group) who had treatment or health checkup in Hengshui People's Hospital from March 2019 to May 2021 were collected; in addition, MDS cell line SKM-1 was also collected for this study. The mRNA expression levels of miR-17-5p and SETD2 in MDS bone marrow and SKM-1 cells were detected by qPCR. The targeting relationship between miR-17-5p and SETD2 was verified using dual-luciferase reporter gene assay. si-miR-NC, si-miR-17-5p, miR-NC, miR-17-5p mimics, pcDNA, pcDNA[1]SETD2, si-miR-17-5p+si-NC, and si-miR-17-5p+si-SETD2 were respectively transfected into SKM-1 cells using liposome transfection technology. CCK-8 method and flow cytometry were used to detect proliferation and apoptosis of SKM-1 cells, and WB method was used to detect the expression of SETD2, C-caspase-3 and C-caspase-9. Results: Compared with the control group, the expression level of miR-17-5p in bone marrow of MDS group significantly elevated, while the mRNA and protein expression levels of SETD2 significantly decreased (all P<0.01). Compared with si-miR-NC group, the proliferation ability of SKM-1 cells in si-miR-17-5p group decreased significantly, while the apoptosis rate and the expression of C-caspase-3 and C-caspase-9 increased significantly (all P<0.01).miR-17-5p significantly inhibited the luciferase activity of the cells with wild-type SETD2 (P<0.01), and negatively regulated the expression of SETD2. Overexpression of SETD2 significantly inhibited the proliferation and promoted apoptosis of SKM-1 cells, while simultaneously interfering with the expression of SETD2 partially reversed the proliferation inhibition and apoptosis promotion effect of miR-17-5p knockdown on SKM-1 cells. Conclusion: miR-17-5p is highly expressed in MDS bone marrow. Knockdown of miR-17-5p can inhibit proliferation and promote apoptosis of SKM-1 cells, the mechanism of which may be related to the negative regulation of SETD2 expression by miR-17-5p.
Objective: To investigate the effect of miR-17-5p and SET domain containing 2 (SETD2) on proliferation and apoptosis of myelodysplastic syndrome (MDS) SKM-1 cells and its mechanism. Methods: Bone marrow samples of 35 MDS patients (MDS group) and 35 healthy persons (control group) who had treatment or health checkup in Hengshui People's Hospital from March 2019 to May 2021 were collected; in addition, MDS cell line SKM-1 was also collected for this study. The mRNA expression levels of miR-17-5p and SETD2 in MDS bone marrow and SKM-1 cells were detected by qPCR. The targeting relationship between miR-17-5p and SETD2 was verified using dual-luciferase reporter gene assay. si-miR-NC, si-miR-17-5p, miR-NC, miR-17-5p mimics, pcDNA, pcDNA[1]SETD2, si-miR-17-5p+si-NC, and si-miR-17-5p+si-SETD2 were respectively transfected into SKM-1 cells using liposome transfection technology. CCK-8 method and flow cytometry were used to detect proliferation and apoptosis of SKM-1 cells, and WB method was used to detect the expression of SETD2, C-caspase-3 and C-caspase-9. Results: Compared with the control group, the expression level of miR-17-5p in bone marrow of MDS group significantly elevated, while the mRNA and protein expression levels of SETD2 significantly decreased (all P<0.01). Compared with si-miR-NC group, the proliferation ability of SKM-1 cells in si-miR-17-5p group decreased significantly, while the apoptosis rate and the expression of C-caspase-3 and C-caspase-9 increased significantly (all P<0.01).miR-17-5p significantly inhibited the luciferase activity of the cells with wild-type SETD2 (P<0.01), and negatively regulated the expression of SETD2. Overexpression of SETD2 significantly inhibited the proliferation and promoted apoptosis of SKM-1 cells, while simultaneously interfering with the expression of SETD2 partially reversed the proliferation inhibition and apoptosis promotion effect of miR-17-5p knockdown on SKM-1 cells. Conclusion: miR-17-5p is highly expressed in MDS bone marrow. Knockdown of miR-17-5p can inhibit proliferation and promote apoptosis of SKM-1 cells, the mechanism of which may be related to the negative regulation of SETD2 expression by miR-17-5p.
2022, 29(1):37-42.
DOI: 10.3872/j.issn.1007-385X.2022.01.006
Abstract:
Objective: To investigate the molecular mechanism by which miR-502-3p regulates the proliferation, cell cycle and apoptosis of colorectal cancer stem cells (CCSCs) by targeting GTP binding protein 2 (GTPBP2) gene. Methods: The immunomagnetic bead sorting technique was used to sort CCSCs (CD133+CD44+ cells and CD133-CD44- cells) from colorectal cancer HCT116 cells, and the expression level of miR-502-3p in the sorted cells was detected by qPCR. CD133+CD44+ cells were divided into different groups according to different transfections using liposome method, namely miR-NC group, miR-502-3p group,si-miR-NC group, si-miR-502-3p group, miR-502-3p+vector group and miR-502-3p+GTPBP2 group. The mRNA expression levels of miR-502-3p and GTPBP2 in cells were detected using qPCR method. The proliferation rate, cell cycle and apoptosis rate were detected by MTT assay and flow cytometry, and the protein expression levels of Ki67, CDK1, Bcl2, BAX and GTPBP2 were detected by WB. Dual-luciferase reporter gene assay adopted to verify the targeting relationship between miR-502-3p and GTPBP2 gene. Results: The expression level of miR-502-3p in CD133+CD44+ cells was significantly lower than that in CD133-CD44- cells (P<0.01). Compared with the miR-NC group, the cell proliferation rate and the proportion of S phase cells were significantly reduced (all P<0.01), the apoptosis rate and proportion of cells in G0/G1 phase were significantly increased (all P<0.01), the protein expression of Ki67, CDK1 and Bcl2 was significantly down-regulated (all P<0.01), and BAX protein expression was significantly up-regulated (P<0.01) in the miR-502-3p group. miR-502-3p targetedly regulated the expression of GTPBP2. Overexpression of GTPBP2 could reverse the effects of up-regulation of miR-502-3p on the proliferation, cell cycle and apoptosis of CCSCs. Conclusion: Up-regulating the expression of miR-502-3p can inhibits the proliferation, arrests the cell cycle, and induces the apoptosis of CCSCs. The mechanism may be related to the overexpression of GTPBP2 gene.
Objective: To investigate the molecular mechanism by which miR-502-3p regulates the proliferation, cell cycle and apoptosis of colorectal cancer stem cells (CCSCs) by targeting GTP binding protein 2 (GTPBP2) gene. Methods: The immunomagnetic bead sorting technique was used to sort CCSCs (CD133+CD44+ cells and CD133-CD44- cells) from colorectal cancer HCT116 cells, and the expression level of miR-502-3p in the sorted cells was detected by qPCR. CD133+CD44+ cells were divided into different groups according to different transfections using liposome method, namely miR-NC group, miR-502-3p group,si-miR-NC group, si-miR-502-3p group, miR-502-3p+vector group and miR-502-3p+GTPBP2 group. The mRNA expression levels of miR-502-3p and GTPBP2 in cells were detected using qPCR method. The proliferation rate, cell cycle and apoptosis rate were detected by MTT assay and flow cytometry, and the protein expression levels of Ki67, CDK1, Bcl2, BAX and GTPBP2 were detected by WB. Dual-luciferase reporter gene assay adopted to verify the targeting relationship between miR-502-3p and GTPBP2 gene. Results: The expression level of miR-502-3p in CD133+CD44+ cells was significantly lower than that in CD133-CD44- cells (P<0.01). Compared with the miR-NC group, the cell proliferation rate and the proportion of S phase cells were significantly reduced (all P<0.01), the apoptosis rate and proportion of cells in G0/G1 phase were significantly increased (all P<0.01), the protein expression of Ki67, CDK1 and Bcl2 was significantly down-regulated (all P<0.01), and BAX protein expression was significantly up-regulated (P<0.01) in the miR-502-3p group. miR-502-3p targetedly regulated the expression of GTPBP2. Overexpression of GTPBP2 could reverse the effects of up-regulation of miR-502-3p on the proliferation, cell cycle and apoptosis of CCSCs. Conclusion: Up-regulating the expression of miR-502-3p can inhibits the proliferation, arrests the cell cycle, and induces the apoptosis of CCSCs. The mechanism may be related to the overexpression of GTPBP2 gene.
2022, 29(1):43-49.
DOI: 10.3872/j.issn.1007-385X.2022.01.007
Abstract:
Objective: To investigate the expression and clinical significance of bridging intergrator 1 (BIN1) in epithelial ovarian cancer (EOC) tissues, and to explore its effect on the proliferation, migration and invasion of ovarian cancer A2780 cells. Methods: The tumor tissues of 67 patients with EOC who underwent tumor resection in the Fourth Hospital of Hebei Medical University from July 2017 to January 2018 were collected. Ovarian tissues resected from 30 non-tumor patients with other gynecological diseases during the same period were collected as normal controls. Immunohistochemical staining was used to detect the expression of BIN1 in EOC tissues and non-tumor ovarian tissues. χ2 test was used to analyze the correlation between the expression of BIN1 and various clinicopathological factors of EOC patients. Kaplan-Meier method was used to analyze the correlation between the expression of BIN1 and disease-free survival (DFS) or overall survival (OS) of patients. The mRNA and protein expression levels of BIN1 in EOC cells (SKOV3 and A2780) and human ovarian epithelial IOSE80 cells were detected by qPCR and WB. The BIN1 plasmid CMV-MCS-GFP[1]SV40-neomycin-BIN1 and the empty plasmid CMV-MCS-GFP-SV40-Neomycin were respectively transfected into A2780 cells to construct BIN1 overexpressed cells and its control. The mRNA and protein expression levels of BIN1 in transfected cells were detected by qPCR and WB, respectively. The effects of BIN1 overexpression on the proliferation, migration and invasion of A2780 cells were detected by CCK-8 test, wound-healing assay and Transwell test, respectively. Results: The positive expression rate of BIN1 in EOC tissues was significantly lower than that in normal ovarian tissues (P<0.01). Low BIN1 expression was positively related with advanced postoperative pathological stage, worse histological grade, lymph node metastasis and peritoneal metastasis in patients with EOC (all P<0.05). The DFS and OS of the patients in the low BIN1 expression group were shorter than those in the high BIN1 expression group (all P<0.05). The mRNA and protein expression levels of BIN1 in SKOV3 and A2780 cells were significantly lower than those in IOSE80 cells (all P<0.01). Overexpression of BIN1 significantly inhibited the proliferation, migration and invasion of A2780 cells (P<0.05 or P<0.01). Conclusion: BIN1 is lowly expressed in EOC tissues and cells, and its low expression is related to the poor prognosis of EOC patients. Overexpression of BIN1 can inhibit the proliferation, migration and invasion ability of ovarian cancer A2780 cells.
Objective: To investigate the expression and clinical significance of bridging intergrator 1 (BIN1) in epithelial ovarian cancer (EOC) tissues, and to explore its effect on the proliferation, migration and invasion of ovarian cancer A2780 cells. Methods: The tumor tissues of 67 patients with EOC who underwent tumor resection in the Fourth Hospital of Hebei Medical University from July 2017 to January 2018 were collected. Ovarian tissues resected from 30 non-tumor patients with other gynecological diseases during the same period were collected as normal controls. Immunohistochemical staining was used to detect the expression of BIN1 in EOC tissues and non-tumor ovarian tissues. χ2 test was used to analyze the correlation between the expression of BIN1 and various clinicopathological factors of EOC patients. Kaplan-Meier method was used to analyze the correlation between the expression of BIN1 and disease-free survival (DFS) or overall survival (OS) of patients. The mRNA and protein expression levels of BIN1 in EOC cells (SKOV3 and A2780) and human ovarian epithelial IOSE80 cells were detected by qPCR and WB. The BIN1 plasmid CMV-MCS-GFP[1]SV40-neomycin-BIN1 and the empty plasmid CMV-MCS-GFP-SV40-Neomycin were respectively transfected into A2780 cells to construct BIN1 overexpressed cells and its control. The mRNA and protein expression levels of BIN1 in transfected cells were detected by qPCR and WB, respectively. The effects of BIN1 overexpression on the proliferation, migration and invasion of A2780 cells were detected by CCK-8 test, wound-healing assay and Transwell test, respectively. Results: The positive expression rate of BIN1 in EOC tissues was significantly lower than that in normal ovarian tissues (P<0.01). Low BIN1 expression was positively related with advanced postoperative pathological stage, worse histological grade, lymph node metastasis and peritoneal metastasis in patients with EOC (all P<0.05). The DFS and OS of the patients in the low BIN1 expression group were shorter than those in the high BIN1 expression group (all P<0.05). The mRNA and protein expression levels of BIN1 in SKOV3 and A2780 cells were significantly lower than those in IOSE80 cells (all P<0.01). Overexpression of BIN1 significantly inhibited the proliferation, migration and invasion of A2780 cells (P<0.05 or P<0.01). Conclusion: BIN1 is lowly expressed in EOC tissues and cells, and its low expression is related to the poor prognosis of EOC patients. Overexpression of BIN1 can inhibit the proliferation, migration and invasion ability of ovarian cancer A2780 cells.
2022, 29(1):50-54.
DOI: 10.3872/j.issn.1007-385X.2022.01.008
Abstract:
Objective: To investigate the expression of programmed death protein 1 (PD-1) and NOD-like receptor protein 3 (NLRP3) in follicular thyroid carcinoma (FTC) tissues and their relationship with clinicopathological features and prognosis of patients.Methods: A total of 60 pairs of cancer tissues and corresponding para-cancerous tissues that surgically resected from patients with FTC at the Second Affiliated Hospital of Fujian Medical University from January 2015 to June 2020 were collected for this study. The positive expression rate of PD-1 and NLRP3 was detected by immunohistochemical staining in the cancer and para-cancerous tissues.The relationship between the expression of PD-1, NLRP3 and the clinicopathological characteristics of FTC patients was analyzed by χ2 test or Fisher's exact test. Pearson correlation analysis was used to analyze the relationship between the expression of PD-1 and NLRP3,and Kaplan-Meier survival analysis and Logistic regression analysis were used to analyze the relationship between the expression of PD-1, NLRP3 and the prognosis of FTC patients. Results: High positive expression rates of PD-1 and NLRP3 were observed (46.67%and 63.33%) in the FTC tissues. The expression of PD-1 was significantly correlated with tumor stage, tumor diameter, vascular invasion and recurrence status of FTC patients (all P<0.05), while the expression of NLRP3 was significantly correlated with tumor diameter, vascular invasion, extra-thyroid infiltration and recurrence status of the patients (all P<0.05). The expression of PD-1 was negatively correlated with NLRP3 level. PD-1 was correlated with a better prognosis of patients, while NLRP3 was an independent risk factor for disease recurrence. Conclusion: PD-1 and NLRP3 have high positive expression rate in FTC tissues. The former is associated with better prognosis, while the latter is an independent risk factor for disease recurrence, and the two are negatively correlated.
Objective: To investigate the expression of programmed death protein 1 (PD-1) and NOD-like receptor protein 3 (NLRP3) in follicular thyroid carcinoma (FTC) tissues and their relationship with clinicopathological features and prognosis of patients.Methods: A total of 60 pairs of cancer tissues and corresponding para-cancerous tissues that surgically resected from patients with FTC at the Second Affiliated Hospital of Fujian Medical University from January 2015 to June 2020 were collected for this study. The positive expression rate of PD-1 and NLRP3 was detected by immunohistochemical staining in the cancer and para-cancerous tissues.The relationship between the expression of PD-1, NLRP3 and the clinicopathological characteristics of FTC patients was analyzed by χ2 test or Fisher's exact test. Pearson correlation analysis was used to analyze the relationship between the expression of PD-1 and NLRP3,and Kaplan-Meier survival analysis and Logistic regression analysis were used to analyze the relationship between the expression of PD-1, NLRP3 and the prognosis of FTC patients. Results: High positive expression rates of PD-1 and NLRP3 were observed (46.67%and 63.33%) in the FTC tissues. The expression of PD-1 was significantly correlated with tumor stage, tumor diameter, vascular invasion and recurrence status of FTC patients (all P<0.05), while the expression of NLRP3 was significantly correlated with tumor diameter, vascular invasion, extra-thyroid infiltration and recurrence status of the patients (all P<0.05). The expression of PD-1 was negatively correlated with NLRP3 level. PD-1 was correlated with a better prognosis of patients, while NLRP3 was an independent risk factor for disease recurrence. Conclusion: PD-1 and NLRP3 have high positive expression rate in FTC tissues. The former is associated with better prognosis, while the latter is an independent risk factor for disease recurrence, and the two are negatively correlated.
2022, 29(1):55-62.
DOI: 10.3872/j.issn.1007-385X.2022.01.009
Abstract:
Objective: To investigate the expression of methyltransferase-like protein 7B (METTL7B) in glioma tissues and its correlation with clinicopathological features and prognosis of patients. Methods: The differential expression of METTL7B gene in glioma and normal brain tissues was analyzed based on the glioma data in CGGA database and the normal brain tissue data in the GTEx database, which was verified using the GEPIA database and immunohistochemical staining. Kaplan-Meier survival analysis, univariate and multivariate Cox analyses and ROC curve analysis were used to evaluate the prognostic value of METTL7B for the patients with glioma. CGGA database was used to analyze the correlation between the METTL7B expression and the clinicopathological characteristics of patients with glioma. CIBERSORT and TIMER databases were adopted to analyze the tumor immune cell infiltration.The genes closely related to METTL7B were identified through gene co-expression analysis. KEGG pathway enrichment analysis and GO function enrichment analysis were also performed. Results: METTL7B was significantly upregulated in glioma tissues (all P<0.05), and its high expression was an independent adverse prognostic factor for glioma patients. High METTL7B expression was significantly related to old age (>41 years old), advanced tumor grade, tumor recurrence or secondary tumors, IDH wild-type, 1p19q non-codeletion and tumor malignant pathology (all P<0.01). METTL7B expression was related to immune cells, such as B cells, CD4+T cells, CD8+ T cells, monocytes, neutrophils, macrophages, and activated mast cells (all P<0.05). The KEGG pathway enrichment and the GO function analysis showed that tumor-related signaling pathways and multiple immune responses were significantly enriched in the METTL7B high expression phenotypes (all P<0.05). Gene co-expression analysis results showed that METTL7B expression was positively correlated with the expression of TNFRSF12A, CHI3L1 and EMP3 (r=0.807, 0.804, 0.783, all P<0.01), but negatively correlated with the expression of ELFN2, REPS2, and SHANK2 (r=-0.642,-0.627,-0.602, all P<0.01). Conclusion: The upregulation of METTL7B expression in glioma tissues is an indicator of poor prognosis, which is related to tumor immune infiltration.
Objective: To investigate the expression of methyltransferase-like protein 7B (METTL7B) in glioma tissues and its correlation with clinicopathological features and prognosis of patients. Methods: The differential expression of METTL7B gene in glioma and normal brain tissues was analyzed based on the glioma data in CGGA database and the normal brain tissue data in the GTEx database, which was verified using the GEPIA database and immunohistochemical staining. Kaplan-Meier survival analysis, univariate and multivariate Cox analyses and ROC curve analysis were used to evaluate the prognostic value of METTL7B for the patients with glioma. CGGA database was used to analyze the correlation between the METTL7B expression and the clinicopathological characteristics of patients with glioma. CIBERSORT and TIMER databases were adopted to analyze the tumor immune cell infiltration.The genes closely related to METTL7B were identified through gene co-expression analysis. KEGG pathway enrichment analysis and GO function enrichment analysis were also performed. Results: METTL7B was significantly upregulated in glioma tissues (all P<0.05), and its high expression was an independent adverse prognostic factor for glioma patients. High METTL7B expression was significantly related to old age (>41 years old), advanced tumor grade, tumor recurrence or secondary tumors, IDH wild-type, 1p19q non-codeletion and tumor malignant pathology (all P<0.01). METTL7B expression was related to immune cells, such as B cells, CD4+T cells, CD8+ T cells, monocytes, neutrophils, macrophages, and activated mast cells (all P<0.05). The KEGG pathway enrichment and the GO function analysis showed that tumor-related signaling pathways and multiple immune responses were significantly enriched in the METTL7B high expression phenotypes (all P<0.05). Gene co-expression analysis results showed that METTL7B expression was positively correlated with the expression of TNFRSF12A, CHI3L1 and EMP3 (r=0.807, 0.804, 0.783, all P<0.01), but negatively correlated with the expression of ELFN2, REPS2, and SHANK2 (r=-0.642,-0.627,-0.602, all P<0.01). Conclusion: The upregulation of METTL7B expression in glioma tissues is an indicator of poor prognosis, which is related to tumor immune infiltration.
10 Research progress on the role of amino acid metabolism in tumor microenvironment and immunotherapy
2022, 29(1):63-69.
DOI: 10.3872/j.issn.1007-385X.2022.01.010
Abstract:
氨基酸是人体主要营养物质，更是肿瘤微环境（TME）中免疫细胞和肿瘤细胞重要的代谢物质，不同氨基酸在TME中 发挥的作用不尽相同。免疫细胞可以利用氨基酸进行增殖、活化和发挥抗肿瘤作用，而肿瘤细胞同样可以将氨基酸用于其增殖、 侵袭和免疫逃逸，氨基酸在两者之间的代谢平衡直接影响TME中的免疫状态。在某些条件的作用下，肿瘤细胞改变TME中氨基 酸代谢平衡，重新分配后的氨基酸向肿瘤细胞倾斜，重塑后的TME将更适合肿瘤细胞生长。免疫治疗在调节氨基酸代谢中同样 发挥作用。免疫检查点负性调控分子抑制效应T细胞氨基酸摄入以抑制其新陈代谢，进而抑制抗肿瘤免疫应答，应用相应抗体 治疗不仅能增强T细胞杀伤作用，更可以重新平衡TME中氨基酸代谢。氨基酸饥饿疗法也可增加部分免疫治疗的疗效。
氨基酸是人体主要营养物质，更是肿瘤微环境（TME）中免疫细胞和肿瘤细胞重要的代谢物质，不同氨基酸在TME中 发挥的作用不尽相同。免疫细胞可以利用氨基酸进行增殖、活化和发挥抗肿瘤作用，而肿瘤细胞同样可以将氨基酸用于其增殖、 侵袭和免疫逃逸，氨基酸在两者之间的代谢平衡直接影响TME中的免疫状态。在某些条件的作用下，肿瘤细胞改变TME中氨基 酸代谢平衡，重新分配后的氨基酸向肿瘤细胞倾斜，重塑后的TME将更适合肿瘤细胞生长。免疫治疗在调节氨基酸代谢中同样 发挥作用。免疫检查点负性调控分子抑制效应T细胞氨基酸摄入以抑制其新陈代谢，进而抑制抗肿瘤免疫应答，应用相应抗体 治疗不仅能增强T细胞杀伤作用，更可以重新平衡TME中氨基酸代谢。氨基酸饥饿疗法也可增加部分免疫治疗的疗效。
2022, 29(1):70-74.
DOI: 10.3872/j.issn.1007-385X.2022.01.011
Abstract:
在肿瘤微环境（TME）中，肿瘤来源外泌体（TDE）可被成纤维细胞摄取，并诱导后者分化为肿瘤相关成纤维细胞 （CAF），而CAF又可通过多种机制促进肿瘤的发展。了解TDE诱导CAF形成的作用机制，对基于TME理念的靶向治疗具有重 要意义。目前，绝大多数研究均是采用超速离心或试剂盒提取等方法从人源性肿瘤细胞中提取TDE，将其与成纤维细胞进行共 培养，再通过检测α-平滑肌肌动蛋白和成纤维细胞活化蛋白等特征蛋白的表达以鉴定CAF。进一步机制研究发现，TDE所携带 的某些蛋白或miRNA可通过转化生长因子-β/SMAD、肿瘤坏死因子-α/核因子-κB、细胞外调节蛋白激酶1/2/血管细胞黏附蛋白-1 和Ras超家族三磷酸鸟苷激酶-35/MMP1/MMP3等多条通路促进CAF的生成，其结果是促进肿瘤细胞的增殖和迁移、破坏细胞外 基质成分、促进微血管生成，以及提高小鼠体内的成瘤能力。
在肿瘤微环境（TME）中，肿瘤来源外泌体（TDE）可被成纤维细胞摄取，并诱导后者分化为肿瘤相关成纤维细胞 （CAF），而CAF又可通过多种机制促进肿瘤的发展。了解TDE诱导CAF形成的作用机制，对基于TME理念的靶向治疗具有重 要意义。目前，绝大多数研究均是采用超速离心或试剂盒提取等方法从人源性肿瘤细胞中提取TDE，将其与成纤维细胞进行共 培养，再通过检测α-平滑肌肌动蛋白和成纤维细胞活化蛋白等特征蛋白的表达以鉴定CAF。进一步机制研究发现，TDE所携带 的某些蛋白或miRNA可通过转化生长因子-β/SMAD、肿瘤坏死因子-α/核因子-κB、细胞外调节蛋白激酶1/2/血管细胞黏附蛋白-1 和Ras超家族三磷酸鸟苷激酶-35/MMP1/MMP3等多条通路促进CAF的生成，其结果是促进肿瘤细胞的增殖和迁移、破坏细胞外 基质成分、促进微血管生成，以及提高小鼠体内的成瘤能力。
2022, 29(1):75-79.
DOI: 10.3872/j.issn.1007-385X.2022.01.012
Abstract:
肿瘤细胞主要通过有氧糖酵解获取能量。然而，肿瘤微环境（TME）中的成熟T细胞也会发生代谢重编程，通过有氧 糖酵解获取能量，维持T细胞增殖和活性。快速增殖的肿瘤细胞可与TME中的其他细胞竞争营养物质，导致T细胞能量供给的 相对缺乏和糖酵解水平的低下，从而影响T细胞抗肿瘤作用的发挥。T细胞葡萄糖缺乏可诱导PD-1分子的过表达，进而介导免 疫耐受的发生。此外，PD-L1/PD-1的结合可激活T细胞并抑制糖酵解反应，降低T细胞的杀伤活性。c-Myc和缺氧诱导因子1α 等分子对T细胞代谢具有重要调控作用。恢复TME中的T细胞代谢和抗肿瘤效应，具有重要的转化医学价值。本文综述了近年 来肿瘤细胞与T细胞糖代谢重编程相互作用方面的研究进展，以及改善肿瘤免疫治疗的潜在策略。
肿瘤细胞主要通过有氧糖酵解获取能量。然而，肿瘤微环境（TME）中的成熟T细胞也会发生代谢重编程，通过有氧 糖酵解获取能量，维持T细胞增殖和活性。快速增殖的肿瘤细胞可与TME中的其他细胞竞争营养物质，导致T细胞能量供给的 相对缺乏和糖酵解水平的低下，从而影响T细胞抗肿瘤作用的发挥。T细胞葡萄糖缺乏可诱导PD-1分子的过表达，进而介导免 疫耐受的发生。此外，PD-L1/PD-1的结合可激活T细胞并抑制糖酵解反应，降低T细胞的杀伤活性。c-Myc和缺氧诱导因子1α 等分子对T细胞代谢具有重要调控作用。恢复TME中的T细胞代谢和抗肿瘤效应，具有重要的转化医学价值。本文综述了近年 来肿瘤细胞与T细胞糖代谢重编程相互作用方面的研究进展，以及改善肿瘤免疫治疗的潜在策略。
2022, 29(1):80-85.
DOI: 10.3872/j.issn.1007-385X.2022.01.013
Abstract:
消化系统恶性肿瘤是一类发病率高、侵袭性强、预后差的临床常见恶性肿瘤，尽管传统的抗肿瘤疗法取得了很大进 步，但是多数患者的预后仍然较差。随着分子肿瘤学、肿瘤免疫学、抗体药物以及生物学技术的发展，消化系统恶性肿瘤迎来免 疫治疗的新时代。肿瘤免疫治疗应用免疫学原理，通过激发和增强机体抗肿瘤免疫应答能力，协同机体免疫系统杀伤肿瘤细胞 并抑制肿瘤生长。免疫治疗具有肿瘤靶向杀伤、安全持久等特点，以免疫检查点抑制剂、肿瘤疫苗、过继细胞疗法为代表的一系 列免疫疗法在消化系统恶性肿瘤的临床前研究和临床试验中都显示出良好的应用前景，有望成为主流的肿瘤治疗方法。了解消 化系统恶性肿瘤免疫治疗现状，熟知正在进行的临床试验及安全性和应对策略，对提高肿瘤的临床治疗效果具有重要意义。
消化系统恶性肿瘤是一类发病率高、侵袭性强、预后差的临床常见恶性肿瘤，尽管传统的抗肿瘤疗法取得了很大进 步，但是多数患者的预后仍然较差。随着分子肿瘤学、肿瘤免疫学、抗体药物以及生物学技术的发展，消化系统恶性肿瘤迎来免 疫治疗的新时代。肿瘤免疫治疗应用免疫学原理，通过激发和增强机体抗肿瘤免疫应答能力，协同机体免疫系统杀伤肿瘤细胞 并抑制肿瘤生长。免疫治疗具有肿瘤靶向杀伤、安全持久等特点，以免疫检查点抑制剂、肿瘤疫苗、过继细胞疗法为代表的一系 列免疫疗法在消化系统恶性肿瘤的临床前研究和临床试验中都显示出良好的应用前景，有望成为主流的肿瘤治疗方法。了解消 化系统恶性肿瘤免疫治疗现状，熟知正在进行的临床试验及安全性和应对策略，对提高肿瘤的临床治疗效果具有重要意义。
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- 《中国肿瘤生物治疗杂志》
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- 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
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.