Mobile website
Volume 29,Issue 9,2022 Table of Contents
2022, 29(9):781-790.
DOI: 10.3872/j.issn.1007-385X.2022.09.001
Abstract:
In recent years, T-lymphocyte-based immune cell therapies have achieved remarkable progress in hematologic tumors and some solid tumors. However, there still remain many challenges in immune cell therapies for solid tumors, such as antigen heterogeneity, immune evasion, poor immune cell infiltration, immunosuppressive microenvironment, metabolic obstructive microenvironment and T cell exhaustion, limiting further improvement in immune cell therapies for solid tumors. The effectiveness of immune cells in solid tumor therapy can be efficiently improved by searching for new antigens, designing multi-target CARs, overexpressing chemokine receptors and cytokines, knocking down inhibitory signaling molecules, enhancing T cell metabolic capacity, combining immune checkpoint inhibitors and epigenetic modifications. This article reviews systematically the current status of research, challenges and solution strategies of immune cell therapies for solid tumors, such as tumor-infiltrating lymphocyte (TIL) therapy, TCR-T (T cell receptor-engineered T) cell therapy and CAR-T (chimeric antigen receptor T) cell therapy.
In recent years, T-lymphocyte-based immune cell therapies have achieved remarkable progress in hematologic tumors and some solid tumors. However, there still remain many challenges in immune cell therapies for solid tumors, such as antigen heterogeneity, immune evasion, poor immune cell infiltration, immunosuppressive microenvironment, metabolic obstructive microenvironment and T cell exhaustion, limiting further improvement in immune cell therapies for solid tumors. The effectiveness of immune cells in solid tumor therapy can be efficiently improved by searching for new antigens, designing multi-target CARs, overexpressing chemokine receptors and cytokines, knocking down inhibitory signaling molecules, enhancing T cell metabolic capacity, combining immune checkpoint inhibitors and epigenetic modifications. This article reviews systematically the current status of research, challenges and solution strategies of immune cell therapies for solid tumors, such as tumor-infiltrating lymphocyte (TIL) therapy, TCR-T (T cell receptor-engineered T) cell therapy and CAR-T (chimeric antigen receptor T) cell therapy.
2022, 29(9):791-796.
DOI: 10.3872/j.issn.1007-385X.2022.09.002
Abstract:
Multiple myeloma，the second most common hematologic malignancy, is caused by the abnormal growth of plasma cells in bone marrow. The increasing number of biological treatment methods provides new ideas for the treatment of multiple myeloma, and CAR-T cell therapy brings the possibility of a cure for relapse/refractory multiple myeloma patients. CAR-T cells targeting different multipke myeloma specific molecules have shown good results in clinical trials. However, insufficient efficacy duration and disease recurrence are still associated with CAR-T cell therapy, which may be associated with persistent CAR-T cells deficiency, loss of tumor cell surface antigen expression, antigen escape and impaired T cell activity in the immunosuppressive microenvironment. Clinical studies have been conducted to improve the effector function and duration of CAR-T cells by optimizing CAR design, adjusting the preparation process to generate CAR-T cells rich in specific T cell subsets, constructing universal CAR-T cells derived from healthy volunteers and introducing modification genes to regulate the immunosuppressive microenvironment or improve the proliferation capacity of CAR-T cells. And clinical studies have been conducted to improve the safety of CAR-T cell therapy by reducing the immunogenicity of antibodies in CAR structures and introducing switching mechanisms. These studies have injected new vigor into the treatment of multiple myeloma and will provide new methods and options for anti-tumor immunotherapy.
Multiple myeloma，the second most common hematologic malignancy, is caused by the abnormal growth of plasma cells in bone marrow. The increasing number of biological treatment methods provides new ideas for the treatment of multiple myeloma, and CAR-T cell therapy brings the possibility of a cure for relapse/refractory multiple myeloma patients. CAR-T cells targeting different multipke myeloma specific molecules have shown good results in clinical trials. However, insufficient efficacy duration and disease recurrence are still associated with CAR-T cell therapy, which may be associated with persistent CAR-T cells deficiency, loss of tumor cell surface antigen expression, antigen escape and impaired T cell activity in the immunosuppressive microenvironment. Clinical studies have been conducted to improve the effector function and duration of CAR-T cells by optimizing CAR design, adjusting the preparation process to generate CAR-T cells rich in specific T cell subsets, constructing universal CAR-T cells derived from healthy volunteers and introducing modification genes to regulate the immunosuppressive microenvironment or improve the proliferation capacity of CAR-T cells. And clinical studies have been conducted to improve the safety of CAR-T cell therapy by reducing the immunogenicity of antibodies in CAR structures and introducing switching mechanisms. These studies have injected new vigor into the treatment of multiple myeloma and will provide new methods and options for anti-tumor immunotherapy.
2022, 29(9):797-805.
DOI: 10.3872/j.issn.1007-385X.2022.09.003
Abstract:
Objective: To explore the mechanism and clinical significance of carboxypeptidase A4 (CPA4) promoting the proliferation,migration, invasion and epithelial-mesenchymal transformation (EMT) progression of non-small cell lung cancer (NSCLC) cells.Methods: IHC and WB were employed to detect the expression of CPA4 in NSCLC tissues and adjacent tissues of 105 patients with advanced or metastatic NSCLC in Jinan Central Hospital from February 2012 to December 2015 and the expression of CPA4 in NSCLC cells. Chi-square test was used to analyze the association between CPA4 expression and the clinicopathological characteristics of the patients. The relationship between CPA4 expression and the overall survival (OS) of the patients was analyzed by Kaplan-Meier method. H1299 and A549 NSCLC cells with stable overexpression and downexpression of CPA4 were constructed by cell transfection.Changes in the cell proliferation, invasion and migration after overexpression and knockdown of CPA4 were detected by CCK-8 assay,cell colony formation assay, scratch healing assay and Transwell assay. Xenograft tumor models and tail vein‐lung metastasis tumor models of nude mice were established to detect the role of CPA4 in tumor tumorigenesis and metastasis in vivo. Changes in the markers of EMT in the tissues of xenografts were detected by WB and IHC. Results: Compared with paracancer tissues and normal lung epithelial cells, CPA4 was highly expressed in cancer tissues and cancer cells (all P?0.05). The OS of NSCLC patients with high CPA4 expression was significantly shorter than that of patients with low CPA4 expression (P?0.05). High expression of CPA4 was more common in poor differentiation, N2-3 lymph node involvement and TNM stage Ⅳ (P?0.05 or P?0.01). Overexpression of CPA4 promoted H1299 cells, while knockdown of CPA4 inhibited the proliferation, migration and invasion of A549 cells. Overexpression of CPA4 promoted the growth of H1299 cell xenograft tumors and lung metastatic tumors in nude mice. Overexpression of CPA4 promoted the changes of EMT process-related molecules in H1299 cells. Conclusion: CPA4 is highly expressed in NSCLC tissues and cells. Overexpression of CPA4 can induce EMT, promote the proliferation，migration and invasion of NSCLC cells and is related to tumor progression and prognosis. CPA4 is a potential biomarker for predicting relapse and prognosis of NSCLC and can be used for targeted therapy.
Objective: To explore the mechanism and clinical significance of carboxypeptidase A4 (CPA4) promoting the proliferation,migration, invasion and epithelial-mesenchymal transformation (EMT) progression of non-small cell lung cancer (NSCLC) cells.Methods: IHC and WB were employed to detect the expression of CPA4 in NSCLC tissues and adjacent tissues of 105 patients with advanced or metastatic NSCLC in Jinan Central Hospital from February 2012 to December 2015 and the expression of CPA4 in NSCLC cells. Chi-square test was used to analyze the association between CPA4 expression and the clinicopathological characteristics of the patients. The relationship between CPA4 expression and the overall survival (OS) of the patients was analyzed by Kaplan-Meier method. H1299 and A549 NSCLC cells with stable overexpression and downexpression of CPA4 were constructed by cell transfection.Changes in the cell proliferation, invasion and migration after overexpression and knockdown of CPA4 were detected by CCK-8 assay,cell colony formation assay, scratch healing assay and Transwell assay. Xenograft tumor models and tail vein‐lung metastasis tumor models of nude mice were established to detect the role of CPA4 in tumor tumorigenesis and metastasis in vivo. Changes in the markers of EMT in the tissues of xenografts were detected by WB and IHC. Results: Compared with paracancer tissues and normal lung epithelial cells, CPA4 was highly expressed in cancer tissues and cancer cells (all P?0.05). The OS of NSCLC patients with high CPA4 expression was significantly shorter than that of patients with low CPA4 expression (P?0.05). High expression of CPA4 was more common in poor differentiation, N2-3 lymph node involvement and TNM stage Ⅳ (P?0.05 or P?0.01). Overexpression of CPA4 promoted H1299 cells, while knockdown of CPA4 inhibited the proliferation, migration and invasion of A549 cells. Overexpression of CPA4 promoted the growth of H1299 cell xenograft tumors and lung metastatic tumors in nude mice. Overexpression of CPA4 promoted the changes of EMT process-related molecules in H1299 cells. Conclusion: CPA4 is highly expressed in NSCLC tissues and cells. Overexpression of CPA4 can induce EMT, promote the proliferation，migration and invasion of NSCLC cells and is related to tumor progression and prognosis. CPA4 is a potential biomarker for predicting relapse and prognosis of NSCLC and can be used for targeted therapy.
2022, 29(9):806-812.
DOI: 10.3872/j.issn.1007-385X.2022.09.004
Abstract:
Objective: To explore the effect of ethanol extract from euphorbia humifusa (EEEH) on the biological behaviors of human colorectal cancer SW480 cells and its molecular mechanism. Methods: Human colorectal cancer SW480 cells were cultured in vitro,divided into the following experimental groups: Con group, EEEH-L group, EEEH-M group, EEEH-H group,si-NC group, si-circRHOT1 group, EEEH-H+pcDNA group and EEEH-H+pcDNA-circRHOT1 group and transfected with si-NC, si-circRHOT1, pcDNA and PCDNA-circRHOT1 respectively. CCK-8 assay, cell clone formation assay, Transwell assay were used to detect cell proliferation,migration and invasion ability in each group after transfection. qPCR method was employed to detect the expression of circRHOT1 and miR-29a-3p in all the groups of SW480 cells after transfection, and the expressions of MMP-2 and MMP-9 proteins were detected by WB. The dual luciferase reporter experiment was used to detect the targeting relationship between circRHOT1 and miR-29a-3p.Results: Compared with the Con group, the protein expressions of MMP-2 and MMP-9 in SW480 cells in EEEH-L, EEEH-M, and EEEH-H groups were significantly decreased (all P<0.05), the expression of circRHOT1 decreased (all P<0.05) and the expression of miR-29a-3p increased (all P<0.05) in a dose-dependent manner. The cell survival rate, the number of cell clone formation and the number of migration and in asive cells were decreased (all P<0.05). circRHOT1 can target and negatively regulate the expression of miR-29a-3p. Knockdown of circRHOT1 can inhibit the proliferation, migration and invasion of SW480 cells, while overexpression of circRHOT1 can attenuate the inhibitory effects of EEEH on the proliferation, migration and invasion of SW480 cells.Conclusion: EEEH can inhibit the proliferation, migration and invasion of colorectal cancer SW480 cells by regulating the circRHOT1/miR-29a-3p axis.
Objective: To explore the effect of ethanol extract from euphorbia humifusa (EEEH) on the biological behaviors of human colorectal cancer SW480 cells and its molecular mechanism. Methods: Human colorectal cancer SW480 cells were cultured in vitro,divided into the following experimental groups: Con group, EEEH-L group, EEEH-M group, EEEH-H group,si-NC group, si-circRHOT1 group, EEEH-H+pcDNA group and EEEH-H+pcDNA-circRHOT1 group and transfected with si-NC, si-circRHOT1, pcDNA and PCDNA-circRHOT1 respectively. CCK-8 assay, cell clone formation assay, Transwell assay were used to detect cell proliferation,migration and invasion ability in each group after transfection. qPCR method was employed to detect the expression of circRHOT1 and miR-29a-3p in all the groups of SW480 cells after transfection, and the expressions of MMP-2 and MMP-9 proteins were detected by WB. The dual luciferase reporter experiment was used to detect the targeting relationship between circRHOT1 and miR-29a-3p.Results: Compared with the Con group, the protein expressions of MMP-2 and MMP-9 in SW480 cells in EEEH-L, EEEH-M, and EEEH-H groups were significantly decreased (all P<0.05), the expression of circRHOT1 decreased (all P<0.05) and the expression of miR-29a-3p increased (all P<0.05) in a dose-dependent manner. The cell survival rate, the number of cell clone formation and the number of migration and in asive cells were decreased (all P<0.05). circRHOT1 can target and negatively regulate the expression of miR-29a-3p. Knockdown of circRHOT1 can inhibit the proliferation, migration and invasion of SW480 cells, while overexpression of circRHOT1 can attenuate the inhibitory effects of EEEH on the proliferation, migration and invasion of SW480 cells.Conclusion: EEEH can inhibit the proliferation, migration and invasion of colorectal cancer SW480 cells by regulating the circRHOT1/miR-29a-3p axis.
5 Expression and clinical significance of E3 ubiquitin ligase HECW2 in gastric adenocarcinoma tissues
2022, 29(9):813-821.
DOI: 10.3872/j.issn.1007-385X.2022.09.005
Abstract:
Objective: To analyze the expression and clinical significance of E3 ubiquitin ligase (HECW2) in gastric adenocarcinoma using a bioinformatics approach to provide new clues for finding diagnostic and prognostic biomarkers for gastric adenocarcinoma.Methods: The expression of HECW2 in pan-cancer and its relationship with the prognosis of pan-cancer were analyzed by R language.The expression of HECW2 in gastric adenocarcinoma tissues and its relationship with clinicopathological features were analyzed with the help of UCSC Xena, HPA, and Kaplan-Meier Plotter databases. The WB method was used to detect HECW2 protein levels in Chinese gastric adenocarcinoma tissues and their paraneoplastic tissues to verify the analysis results in the database. The relationship between HECW2 and immune infiltration of gastric adenocarcinoma was analyzed with the help of TIMER and Cibersort databases.GO functional analysis and KEGG signaling pathway enrichment analysis and correlation gene analysis were performed for HECW2 in gastric adenocarcinoma by LinkedOmics database. Results: The results of raw signal analysis showed that HECW2 was significantly highly expressed in 12 tumors including gastric adenocarcinoma among 33 different types of tumors (all P<0.05), and the results of WB method showed that HECW2 was also significantly highly expressed in Chinese gastric adenocarcinoma tissues (P<0.05). Higher HECW2 expression level was associated with shorter OS and higher abundance of infiltration of immune cells including CD4+T cells, macrophages, neutrophils and dendritic cells in gastric adenocarcinoma patients (all P?0.01). In addition, HECW2-associated signaling pathways were mainly enriched in extracellular matrix receptor interactions, adherent spots, cell adhesion and oxidative phosphorylation (all P?0.01). Conclusion: HECW2 is significantly overexpressed in gastric adenocarcinoma tissues and is closely related to the poor prognosis and immune invasion of gastric adenocarcinoma, and has great potential as a prognostic biomarker and target therapy for gastric adenocarcinoma.
Objective: To analyze the expression and clinical significance of E3 ubiquitin ligase (HECW2) in gastric adenocarcinoma using a bioinformatics approach to provide new clues for finding diagnostic and prognostic biomarkers for gastric adenocarcinoma.Methods: The expression of HECW2 in pan-cancer and its relationship with the prognosis of pan-cancer were analyzed by R language.The expression of HECW2 in gastric adenocarcinoma tissues and its relationship with clinicopathological features were analyzed with the help of UCSC Xena, HPA, and Kaplan-Meier Plotter databases. The WB method was used to detect HECW2 protein levels in Chinese gastric adenocarcinoma tissues and their paraneoplastic tissues to verify the analysis results in the database. The relationship between HECW2 and immune infiltration of gastric adenocarcinoma was analyzed with the help of TIMER and Cibersort databases.GO functional analysis and KEGG signaling pathway enrichment analysis and correlation gene analysis were performed for HECW2 in gastric adenocarcinoma by LinkedOmics database. Results: The results of raw signal analysis showed that HECW2 was significantly highly expressed in 12 tumors including gastric adenocarcinoma among 33 different types of tumors (all P<0.05), and the results of WB method showed that HECW2 was also significantly highly expressed in Chinese gastric adenocarcinoma tissues (P<0.05). Higher HECW2 expression level was associated with shorter OS and higher abundance of infiltration of immune cells including CD4+T cells, macrophages, neutrophils and dendritic cells in gastric adenocarcinoma patients (all P?0.01). In addition, HECW2-associated signaling pathways were mainly enriched in extracellular matrix receptor interactions, adherent spots, cell adhesion and oxidative phosphorylation (all P?0.01). Conclusion: HECW2 is significantly overexpressed in gastric adenocarcinoma tissues and is closely related to the poor prognosis and immune invasion of gastric adenocarcinoma, and has great potential as a prognostic biomarker and target therapy for gastric adenocarcinoma.
2022, 29(9):822-827.
DOI: 10.3872/j.issn.1007-385X.2022.09.006
Abstract:
Objective: To investigate the expression of human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) and its receptor TMIGD2 (transmembrane and immunoglobulin domain containing 2) in ovarian cancer tissues and analyze the relationship between their expressions and the clinicopathological characteristics and prognosis of ovarian cancer patients.Methods: The expressions of HHLA2 and its receptor TMIGD2 were detected respectively by immunohistochemistry in a tissue microarray (TMA) containing 154 ovarian cancer tissues. The correlation between the expressions and the clinicopathological characteristics of the patients and the impact on prognosis were analyzed. Results: The expression of HHLA2 was associated with the pathological type of ovarian cancer (P<0.05). Kaplan-Merier survival analysis revealed that the high expression of HHLA2 and TMIGD2 was significantly correlated with poor OS in type Ⅰovarian cancer (P<0.05, P<0.01). Univariate Cox proportional hazard model indicated that type Ⅱ, FIGO stage Ⅲ and Ⅳ, lymphatic metastasis and distant metastasis were significantly associated with worse prognosis. Multivariate Cox proportional hazard model showed that TMIGD2 high expression, FIGO stage Ⅲ and Ⅳ, lymphatic metastasis, positive lymphatic metastasis may be independent influencing factors for poor prognosis of ovarian cancer patients and HHLA2 had significant positive correlation with TMIGD2 expression (r=0.603, P<0.01). Conclusion: HHLA2 and its receptor TMIGD2, which are highly expressed in ovarian cancer tissues and significantly correlated with the prognosis of patients, are expected to be prognostic indicators for ovarian cancer patients.
Objective: To investigate the expression of human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) and its receptor TMIGD2 (transmembrane and immunoglobulin domain containing 2) in ovarian cancer tissues and analyze the relationship between their expressions and the clinicopathological characteristics and prognosis of ovarian cancer patients.Methods: The expressions of HHLA2 and its receptor TMIGD2 were detected respectively by immunohistochemistry in a tissue microarray (TMA) containing 154 ovarian cancer tissues. The correlation between the expressions and the clinicopathological characteristics of the patients and the impact on prognosis were analyzed. Results: The expression of HHLA2 was associated with the pathological type of ovarian cancer (P<0.05). Kaplan-Merier survival analysis revealed that the high expression of HHLA2 and TMIGD2 was significantly correlated with poor OS in type Ⅰovarian cancer (P<0.05, P<0.01). Univariate Cox proportional hazard model indicated that type Ⅱ, FIGO stage Ⅲ and Ⅳ, lymphatic metastasis and distant metastasis were significantly associated with worse prognosis. Multivariate Cox proportional hazard model showed that TMIGD2 high expression, FIGO stage Ⅲ and Ⅳ, lymphatic metastasis, positive lymphatic metastasis may be independent influencing factors for poor prognosis of ovarian cancer patients and HHLA2 had significant positive correlation with TMIGD2 expression (r=0.603, P<0.01). Conclusion: HHLA2 and its receptor TMIGD2, which are highly expressed in ovarian cancer tissues and significantly correlated with the prognosis of patients, are expected to be prognostic indicators for ovarian cancer patients.
2022, 29(9):828-833.
DOI: 10.3872/j.issn.1007-385X.2022.09.007
Abstract:
Objective: To observe the clinical efficacy and safety of pembrolizumab plus albumin-bound paclitaxel and nedaplatin as a first-line therapy in patients with advanced esophageal squamous cell carcinoma (ESCC). Methods: 35 patients with advanced ESCC and evaluable foci admitted in Changhai Hospital from March 2020 to September 2021 were included in this study. All patients were given pembrolizumab 200 mg and albumin-bound paclitaxel 130 mg/m2 on day 1 and 8, and nedaplatin 70 mg/m2 on day 1. The treatment was repeated every 21 days. Evaluation of tumor response was performed according to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST1.1). Adverse effects were graded using version 5.0 of the National Cancer Institute Common Toxicity Criteria (NCI-CTC). Results: All 35 patients were available for evaluation, with 4 patients (11.4%) achieving complete response (CR), 21 patients (60.0%) partial response (PR), 10 patients (28.6%) stable disease (SD) and 0 patients progression disease (PD). The objective response rate (ORR) was 71.4%. The disease control rate (DCR) was 100%. The median progression free survival (PFS) was 13.4 months. The main adverse effects include bone marrow suppression, thyroid dysfunction, rash, fever, arthralgia, myalgia and alopecia. Treatment-related adverse events of grade 3 or higher occurred only in 3 patients (8.6%). onclusion: Pembrolizumab plus albuminbound paclitaxel and nedaplatin as a first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety in patients with advanced ESCC. Randomized trials with expanded samples to evaluate this new combination strategy are warranted.
Objective: To observe the clinical efficacy and safety of pembrolizumab plus albumin-bound paclitaxel and nedaplatin as a first-line therapy in patients with advanced esophageal squamous cell carcinoma (ESCC). Methods: 35 patients with advanced ESCC and evaluable foci admitted in Changhai Hospital from March 2020 to September 2021 were included in this study. All patients were given pembrolizumab 200 mg and albumin-bound paclitaxel 130 mg/m2 on day 1 and 8, and nedaplatin 70 mg/m2 on day 1. The treatment was repeated every 21 days. Evaluation of tumor response was performed according to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST1.1). Adverse effects were graded using version 5.0 of the National Cancer Institute Common Toxicity Criteria (NCI-CTC). Results: All 35 patients were available for evaluation, with 4 patients (11.4%) achieving complete response (CR), 21 patients (60.0%) partial response (PR), 10 patients (28.6%) stable disease (SD) and 0 patients progression disease (PD). The objective response rate (ORR) was 71.4%. The disease control rate (DCR) was 100%. The median progression free survival (PFS) was 13.4 months. The main adverse effects include bone marrow suppression, thyroid dysfunction, rash, fever, arthralgia, myalgia and alopecia. Treatment-related adverse events of grade 3 or higher occurred only in 3 patients (8.6%). onclusion: Pembrolizumab plus albuminbound paclitaxel and nedaplatin as a first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety in patients with advanced ESCC. Randomized trials with expanded samples to evaluate this new combination strategy are warranted.
2022, 29(9):834-839.
DOI: 10.3872/j.issn.1007-385X.2022.09.008
Abstract:
结直肠癌（CRC）是最常见、致死率最高的肿瘤之一。嵌合抗原受体T（CAR-T）细胞治疗在CRC中未能重现其在血液 肿瘤和部分实体瘤治疗中获得的成功，其原因除CAR-T细胞治疗本身的研发困境（肿瘤抗原的异质性、特异性抗原的缺少等）外， CRC肿瘤微环境（TME）中存在着多重物理和生化障碍限制了T细胞抗肿瘤作用：TME复杂的脉管系统、纤维性物理屏障影响T 细胞的迁移、抑制性细胞如Treg细胞、髓源性抑制细胞（MDSC）抑制抗肿瘤免疫反应、富集的免疫抑制性细胞因子影响T细胞的 激活、肿瘤细胞通过代谢重编程影响T细胞的存活和功能等。优化CAR结构设计、构建靶向TME中免疫抑制因素的CAR-T细胞 和其他治疗手段联合治疗等策略是克服CAR-T细胞治疗应用于CRC解决低响应率的关键性思路，将为靶向TME的精准免疫治 疗深入发展提供线索和方向。
结直肠癌（CRC）是最常见、致死率最高的肿瘤之一。嵌合抗原受体T（CAR-T）细胞治疗在CRC中未能重现其在血液 肿瘤和部分实体瘤治疗中获得的成功，其原因除CAR-T细胞治疗本身的研发困境（肿瘤抗原的异质性、特异性抗原的缺少等）外， CRC肿瘤微环境（TME）中存在着多重物理和生化障碍限制了T细胞抗肿瘤作用：TME复杂的脉管系统、纤维性物理屏障影响T 细胞的迁移、抑制性细胞如Treg细胞、髓源性抑制细胞（MDSC）抑制抗肿瘤免疫反应、富集的免疫抑制性细胞因子影响T细胞的 激活、肿瘤细胞通过代谢重编程影响T细胞的存活和功能等。优化CAR结构设计、构建靶向TME中免疫抑制因素的CAR-T细胞 和其他治疗手段联合治疗等策略是克服CAR-T细胞治疗应用于CRC解决低响应率的关键性思路，将为靶向TME的精准免疫治 疗深入发展提供线索和方向。
2022, 29(9):840-845.
DOI: 10.3872/j.issn.1007-385X.2022.09.009
Abstract:
作为WHO宣布的Ⅰ类致癌物EBV，其与移植后淋巴组织增生性疾病、霍奇金淋巴瘤（HL）、伯基特淋巴瘤、鼻咽癌、 EBV相关性胃癌等恶性肿瘤的发生相关，且具有作为预后预测指标及治疗靶点的潜能。目前，EBV免疫靶向治疗研究取得了众 多进展，基于EBV疫苗的主动免疫疗法和直接输注EBV-CTL的过继免疫疗法均可激活EBV特异性免疫应答并改善患者生存， PD-1/PD-L1抑制剂和IDO抑制剂联合可通过增强免疫应答、减少免疫逃逸而在EBV相关肿瘤中发挥抗肿瘤作用。此外，某些去 甲基化及去乙酰化药物可靶向作用于EBV阳性肿瘤细胞，诱导EBV病毒基因裂解。未来有望通过靶向治疗及免疫治疗的联合 应用为EBV相关肿瘤患者赢得更好的预后。
作为WHO宣布的Ⅰ类致癌物EBV，其与移植后淋巴组织增生性疾病、霍奇金淋巴瘤（HL）、伯基特淋巴瘤、鼻咽癌、 EBV相关性胃癌等恶性肿瘤的发生相关，且具有作为预后预测指标及治疗靶点的潜能。目前，EBV免疫靶向治疗研究取得了众 多进展，基于EBV疫苗的主动免疫疗法和直接输注EBV-CTL的过继免疫疗法均可激活EBV特异性免疫应答并改善患者生存， PD-1/PD-L1抑制剂和IDO抑制剂联合可通过增强免疫应答、减少免疫逃逸而在EBV相关肿瘤中发挥抗肿瘤作用。此外，某些去 甲基化及去乙酰化药物可靶向作用于EBV阳性肿瘤细胞，诱导EBV病毒基因裂解。未来有望通过靶向治疗及免疫治疗的联合 应用为EBV相关肿瘤患者赢得更好的预后。
10 Research progress in the role and mechanism of MMP-9 in the metastasis of non-small cell lung cancer
2022, 29(9):846-850.
DOI: 10.3872/j.issn.1007-385X.2022.09.010
Abstract:
基质金属蛋白酶-9（MMP-9）是一种关键的基质金属蛋白酶，它能够降解细胞外基质，在肿瘤的侵袭和转移中发挥重 要作用。MMP-9已被国内外多项研究证实在非小细胞肺癌（NSCLC）组织中呈高表达，而与此相关的信号通路有很多，如PI3K/AKT 信号通路、AP-1/NF-κB信号通路、TGF-β1/SIRT1/AMPK信号通路，Wnt/β-catenin信号通路等，其中PI3K/AKT信号通路起主要作 用。高表达的MMP-9可降解细胞外基质，促进肿瘤细胞从原发瘤体脱离，穿过血管内皮细胞进入血液或淋巴并游走至体循环， 最终外渗至新的解剖部位形成转移灶。MMP-9还与免疫逃逸有关，促使机体形成肿瘤适宜的微环境。在NSCLC患者中，MMP-9 的高表达与淋巴结及远处转移相关，还意味着更低的生存率及不良预后。因此，MMP-9有望成为该肿瘤诊治及预后评估的重要 指标。已开发出多种人工合成 MMP 抑制剂，但极少数已应用于临床诊治，相信在不久的将来，MMP 抑制剂或可成为治疗 NSCLC的一种新方式。
基质金属蛋白酶-9（MMP-9）是一种关键的基质金属蛋白酶，它能够降解细胞外基质，在肿瘤的侵袭和转移中发挥重 要作用。MMP-9已被国内外多项研究证实在非小细胞肺癌（NSCLC）组织中呈高表达，而与此相关的信号通路有很多，如PI3K/AKT 信号通路、AP-1/NF-κB信号通路、TGF-β1/SIRT1/AMPK信号通路，Wnt/β-catenin信号通路等，其中PI3K/AKT信号通路起主要作 用。高表达的MMP-9可降解细胞外基质，促进肿瘤细胞从原发瘤体脱离，穿过血管内皮细胞进入血液或淋巴并游走至体循环， 最终外渗至新的解剖部位形成转移灶。MMP-9还与免疫逃逸有关，促使机体形成肿瘤适宜的微环境。在NSCLC患者中，MMP-9 的高表达与淋巴结及远处转移相关，还意味着更低的生存率及不良预后。因此，MMP-9有望成为该肿瘤诊治及预后评估的重要 指标。已开发出多种人工合成 MMP 抑制剂，但极少数已应用于临床诊治，相信在不久的将来，MMP 抑制剂或可成为治疗 NSCLC的一种新方式。
2022, 29(9):851-855.
DOI: 10.3872/j.issn.1007-385X.2022.09.011
Abstract:
黑色素瘤缺乏因子2（AIM2）作为AIM2样受体（ALR）家族成员之一，其和胞质中异常存在的双链DNA进一步组装成 AIM2炎症小体而引起炎症及其相关的包括肿瘤在内的多种疾病。关于AIM2对肿瘤的作用机制，较为明确的是其作为炎症小体 发挥作用，然而AIM2在结肠癌、宫颈癌、肾癌、肝癌等肿瘤中均有差异表达，并且还通过不依赖于AIM2炎症小体的途径发挥促 进或抑制肿瘤的作用，该途径包括PI3K/AKT、EMT、NF-κB以及MAPK/ERK等信号通路。加深基于AIM2对肿瘤发生发展中作 用机制的认识可为肿瘤诊治研究提供新的思路。
黑色素瘤缺乏因子2（AIM2）作为AIM2样受体（ALR）家族成员之一，其和胞质中异常存在的双链DNA进一步组装成 AIM2炎症小体而引起炎症及其相关的包括肿瘤在内的多种疾病。关于AIM2对肿瘤的作用机制，较为明确的是其作为炎症小体 发挥作用，然而AIM2在结肠癌、宫颈癌、肾癌、肝癌等肿瘤中均有差异表达，并且还通过不依赖于AIM2炎症小体的途径发挥促 进或抑制肿瘤的作用，该途径包括PI3K/AKT、EMT、NF-κB以及MAPK/ERK等信号通路。加深基于AIM2对肿瘤发生发展中作 用机制的认识可为肿瘤诊治研究提供新的思路。
2022, 29(9):856-858.
DOI: 10.3872/j.issn.1007-385X.2022.09.012
Abstract:
联系方式
- 《中国肿瘤生物治疗杂志》
- 1994年创刊
- 主办单位：Chinese Society of Immunology, Chinese Anti-cancer Association
- 邮编：200433
- 电话：021-81871002-22
- 电子邮箱：cjcb@biother.cn
- 网址:http://www.biother.cn
- 刊号：ISSN 1007-385X
- CN 31-1725/R
- 国内定价： ￥20元/册
您是第位访问者
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.