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Volume 30,Issue 5,2023 Table of Contents
2023, 30(5):365-372.
DOI: 10.3872/j.issn.1007-385X.2023.05.001
Abstract:
Immune checkpoint blockade (ICB) therapy, represented by PD-1/PD-L1 and CTLA-4, has achieved remarkable efficacy in the treatment of solid tumors; However, only less than 30% of the patients benefit from it, suggesting that there still exists other immune checkpoints molecule-mediated immunosuppression. B7H3 is a member of the B7 immunoglobulin superfamily. Unlike CTLA-4 or PD-1 which is mainly expressed in T cells to mediate their immunosuppression or depletion, B7H3 is not only inducibly expressed in immune cells, but also constitutively highly expressed in various tumor cells and tumor-associated vascular systems. B7H3 not only directly promotes the malignant biological phenotypes of tumor cells by activating multiple signaling pathways, but also indirectly promotes tumor progression, metastasis and drug resistance by remodeling tumor immunosuppressive microenvironment. Therefore, several targeted anti-tumor strategies targeting B7H3, including specific antibodies, antibody-drug conjugation (ADC) and CAR-T, have entered clinical trials and shown promising application prospects. However, in general, the research of B7H3 is still in the exploratory stage. There are still many bottlenecks and challenges to be overcome in the identification of reciprocal receptors, reduction of toxicity, breaking drug resistance, and optimization of combination drug therapy, etc.
Immune checkpoint blockade (ICB) therapy, represented by PD-1/PD-L1 and CTLA-4, has achieved remarkable efficacy in the treatment of solid tumors; However, only less than 30% of the patients benefit from it, suggesting that there still exists other immune checkpoints molecule-mediated immunosuppression. B7H3 is a member of the B7 immunoglobulin superfamily. Unlike CTLA-4 or PD-1 which is mainly expressed in T cells to mediate their immunosuppression or depletion, B7H3 is not only inducibly expressed in immune cells, but also constitutively highly expressed in various tumor cells and tumor-associated vascular systems. B7H3 not only directly promotes the malignant biological phenotypes of tumor cells by activating multiple signaling pathways, but also indirectly promotes tumor progression, metastasis and drug resistance by remodeling tumor immunosuppressive microenvironment. Therefore, several targeted anti-tumor strategies targeting B7H3, including specific antibodies, antibody-drug conjugation (ADC) and CAR-T, have entered clinical trials and shown promising application prospects. However, in general, the research of B7H3 is still in the exploratory stage. There are still many bottlenecks and challenges to be overcome in the identification of reciprocal receptors, reduction of toxicity, breaking drug resistance, and optimization of combination drug therapy, etc.
2023, 30(5):373-379.
DOI: 10.3872/j.issn.1007-385X.2023.05.002
Abstract:
Objective: To develop TCR-T cells with endogenous TCR knockout based on CRISPR/Cas9 gene editing technology, and to identify their cytotoxicity against cancer cells in vitro. Methods: Jurkat cells and CD8+ T cells from the peripheral blood of healthy volunteers were cultured in vitro, and endogenous TCR of the CD8+ T and Jurkat cells was knocked out by CRISPR/Cas9 gene editing technique. Transgenic TCR overexpression lentivirus was prepared and transfected into the CD8+ T and Jurkat cells with endogenous TCR knockout to prepare TCR-T cells. The expression levels of TCR and CD3 in TCR-T cells were detected by multi-color FCM. The killing efficiency of TCR-T cells against HPV16 positive SiHa cells was determined by luciferase activity assay. Results: CRIPSR/Cas9 gene editing technique effectively knocked out TRAC and TRBC genes in the peripheral blood CD8+ T and Jurkat cells, with a knockout efficiency of (81.4±4.5)% , (98.5±0.07)% , respectively. The obtained TCR-T cells after transfections efficiently expressed transgenic TCR, with an expression rate up to (66.0±17.8)% , (97.3±2.6)% . Knockout of endogenous TRAC and TRBC genes effectively enhanced transgenic TCR expression on cell membrane of CD8+ T and Jurkat cells (both P<0.01). Knockout of endogenous TCR enhanced the specific killing of TCR-T cells against HPV16-positive target cells ([71.4±1.0]% vs [35.1±2.0]% , P<0.01).Conclusion: The expression of transgenic TCR in TCR-T cells without endogenous TCR expression was significantly increased, and the targeted killing ability of HPV16-positive cervical cancer SiHa cells was significantly enhanced, which provides experimental basis for improving the clinical therapeutic effect of TCR-T cells.
Objective: To develop TCR-T cells with endogenous TCR knockout based on CRISPR/Cas9 gene editing technology, and to identify their cytotoxicity against cancer cells in vitro. Methods: Jurkat cells and CD8+ T cells from the peripheral blood of healthy volunteers were cultured in vitro, and endogenous TCR of the CD8+ T and Jurkat cells was knocked out by CRISPR/Cas9 gene editing technique. Transgenic TCR overexpression lentivirus was prepared and transfected into the CD8+ T and Jurkat cells with endogenous TCR knockout to prepare TCR-T cells. The expression levels of TCR and CD3 in TCR-T cells were detected by multi-color FCM. The killing efficiency of TCR-T cells against HPV16 positive SiHa cells was determined by luciferase activity assay. Results: CRIPSR/Cas9 gene editing technique effectively knocked out TRAC and TRBC genes in the peripheral blood CD8+ T and Jurkat cells, with a knockout efficiency of (81.4±4.5)% , (98.5±0.07)% , respectively. The obtained TCR-T cells after transfections efficiently expressed transgenic TCR, with an expression rate up to (66.0±17.8)% , (97.3±2.6)% . Knockout of endogenous TRAC and TRBC genes effectively enhanced transgenic TCR expression on cell membrane of CD8+ T and Jurkat cells (both P<0.01). Knockout of endogenous TCR enhanced the specific killing of TCR-T cells against HPV16-positive target cells ([71.4±1.0]% vs [35.1±2.0]% , P<0.01).Conclusion: The expression of transgenic TCR in TCR-T cells without endogenous TCR expression was significantly increased, and the targeted killing ability of HPV16-positive cervical cancer SiHa cells was significantly enhanced, which provides experimental basis for improving the clinical therapeutic effect of TCR-T cells.
2023, 30(5):380-386.
DOI: 10.3872/j.issn.1007-385X.2023.05.003
Abstract:
Objective: To construct programmed death-1 (PD-1)/cytotoxic T lymphocyte antigen-4 (CTLA-4) bispecific antibody (BsAb) based on the target humanized mice, evaluate the anticancer activity of BsAb and its IgG1 isotype and investigate its potential working mechanism. Methods: Different formats and isotypes of PD-1/CTLA-4 antibodies BsAb1, BsAb2 and BsAb3 were constructed, expanded and purified. The target affinity of purified BsAbs were tested by surface plasmon resonance (SPR), and the biological activity of antibodies were tested by luciferase reporter gene assay and FCM. The efficacy of BsAbs was evaluated in vivo based on the MC38-hPD-L1 colon carcinoma cell transplant tumor model in humanized B-hPD-1-hPD-L1-hCTLA-4 mice. The working mechanism of PD-1/CTLA-4 BsAbs in transplant tumor tissues was investigated by tumor-infiltrating lymphocyte (TIL) analysis. Results: Successfully prepared BsAb1, BsAb2, and BsAb3 all demonstrated relatively strong specific affinity to checkpoint targets PD-1 and CTLA-4, showed different levels of blocker efficacy to target pathways, and significantly suppressed the growth of transplant tumors (P<0.05 or P<0.01). BsAb with IgG1 isotype was more potent in vivo than other isotypes (P<0.01). Tumor-infiltrating lymphocyte analysis revealed that BsAb2-IgG1 significantly increased the percentage of cytotoxic T lymphocytes (CTLs) (P<0.05) and significantly decreased the percentage of tumor-infiltrating regulatory T (Treg) cells (P<0.01), thus making the tumor immune microenvironment more conducive in killing tumor cells. However, the ADCC-enhanced Fc mutation isotype of BsAb2-SI can not further improve anti-tumor activity. Conclusion: The IgG1 PD-1/CTLA-4 antibody with Fc effector function has more potent in vivo anticancer efficacy, because it can better remove Treg cells in tumor-infiltrating lymphocytes.
Objective: To construct programmed death-1 (PD-1)/cytotoxic T lymphocyte antigen-4 (CTLA-4) bispecific antibody (BsAb) based on the target humanized mice, evaluate the anticancer activity of BsAb and its IgG1 isotype and investigate its potential working mechanism. Methods: Different formats and isotypes of PD-1/CTLA-4 antibodies BsAb1, BsAb2 and BsAb3 were constructed, expanded and purified. The target affinity of purified BsAbs were tested by surface plasmon resonance (SPR), and the biological activity of antibodies were tested by luciferase reporter gene assay and FCM. The efficacy of BsAbs was evaluated in vivo based on the MC38-hPD-L1 colon carcinoma cell transplant tumor model in humanized B-hPD-1-hPD-L1-hCTLA-4 mice. The working mechanism of PD-1/CTLA-4 BsAbs in transplant tumor tissues was investigated by tumor-infiltrating lymphocyte (TIL) analysis. Results: Successfully prepared BsAb1, BsAb2, and BsAb3 all demonstrated relatively strong specific affinity to checkpoint targets PD-1 and CTLA-4, showed different levels of blocker efficacy to target pathways, and significantly suppressed the growth of transplant tumors (P<0.05 or P<0.01). BsAb with IgG1 isotype was more potent in vivo than other isotypes (P<0.01). Tumor-infiltrating lymphocyte analysis revealed that BsAb2-IgG1 significantly increased the percentage of cytotoxic T lymphocytes (CTLs) (P<0.05) and significantly decreased the percentage of tumor-infiltrating regulatory T (Treg) cells (P<0.01), thus making the tumor immune microenvironment more conducive in killing tumor cells. However, the ADCC-enhanced Fc mutation isotype of BsAb2-SI can not further improve anti-tumor activity. Conclusion: The IgG1 PD-1/CTLA-4 antibody with Fc effector function has more potent in vivo anticancer efficacy, because it can better remove Treg cells in tumor-infiltrating lymphocytes.
2023, 30(5):387-392.
DOI: 10.3872/j.issn.1007-385X.2023.05.004
Abstract:
Objective: To investigate the effects of deguelin on the proliferation and apoptosis of ovarian cancer SKOV3 cells by regulating miR-520a-3p. Methods: The SKOV3 cells were divided into the control group (deguelin 0 μmol/L), low-dose deguelin group (5 μmol/L), medium-dose deguelin group (10 μmol/L), and high-dose deguelin group (20 μmol/L), miR-NC group, miR-520a-3p group, deguelin+anti-miR-NC group and deguelin+anti-miR-520a-3p group. CCK-8, colony formation experiment, flow cytometry and qPCR were used to detect the inhibition rate, the number of clone formation, the apoptosis rate and the miR-520a-3p expression of SKOV3 cells respectively. Results: Compared with the control group, the inhibition rate, the apoptosis rate, miR-520a-3p expression of SKOV3 cells in the deguelin (low, medium, and high dose) groups were significantly increased (all P<0.05), and the number of clone formation was significantly reduced (P<0.05). Compared with the miR-NC group, the inhibitory rate and the apoptosis rate of SKOV3 cells in the miR-520a-3p group were significantly increased (all P<0.05), and the number of clone formation was significantly reduced (P<0.05). Compared with the deguelin+anti-miR-NC group, the inhibition rate and the apoptosis rate of SKOV3 cells in the deguelin+anti-miR-520a-3p group were significantly reduced (all P<0.05), and the number of clone formation was significantly increased (P<0.05). Conclusion: Deguelin inhibited the proliferation potential of ovarian cancer SKOV3 cells and induced cell apoptosis by increasing the expression of miR-520a-3p.
Objective: To investigate the effects of deguelin on the proliferation and apoptosis of ovarian cancer SKOV3 cells by regulating miR-520a-3p. Methods: The SKOV3 cells were divided into the control group (deguelin 0 μmol/L), low-dose deguelin group (5 μmol/L), medium-dose deguelin group (10 μmol/L), and high-dose deguelin group (20 μmol/L), miR-NC group, miR-520a-3p group, deguelin+anti-miR-NC group and deguelin+anti-miR-520a-3p group. CCK-8, colony formation experiment, flow cytometry and qPCR were used to detect the inhibition rate, the number of clone formation, the apoptosis rate and the miR-520a-3p expression of SKOV3 cells respectively. Results: Compared with the control group, the inhibition rate, the apoptosis rate, miR-520a-3p expression of SKOV3 cells in the deguelin (low, medium, and high dose) groups were significantly increased (all P<0.05), and the number of clone formation was significantly reduced (P<0.05). Compared with the miR-NC group, the inhibitory rate and the apoptosis rate of SKOV3 cells in the miR-520a-3p group were significantly increased (all P<0.05), and the number of clone formation was significantly reduced (P<0.05). Compared with the deguelin+anti-miR-NC group, the inhibition rate and the apoptosis rate of SKOV3 cells in the deguelin+anti-miR-520a-3p group were significantly reduced (all P<0.05), and the number of clone formation was significantly increased (P<0.05). Conclusion: Deguelin inhibited the proliferation potential of ovarian cancer SKOV3 cells and induced cell apoptosis by increasing the expression of miR-520a-3p.
2023, 30(5):393-400.
DOI: 10.3872/j.issn.1007-385X.2023.05.005
Abstract:
Objective: To systematically evaluate the safety and efficacy of PD-1/PD-L1 inhibitor-based immunotherapy (hereinafter referred to as "combination immunotherapy") compared with sunitinib in the treatment of advanced renal cell carcinoma (RCC). Methods: Databases such as PubMed, Embase, Cochrane Library, and CNKI were searched from the date of their establishment to October 2022 to collect the randomized controlled trials (RCTs) of combination immunotherapy versus sunitinib for the treatment of advanced renal cell carcinoma (RCC).Two reviewers independently evaluated the quality of included studies, extracted data, and cross-checked the information. Meta-analysis was performed using StataMP16.0 software. Results: A total of 6 RCTs were included. The results of the Meta-analysis showed that: (1)Effectiveness. Compared to sunitinib, combination immunotherapy significantly improved overall survival (HR=0.74, 95% CI [0.67, 0.80], P<0.01) and progression-free survival (HR=0.66, 95% CI [0.51, 0.81], P<0.01) in patients with advanced RCC. (2) Safety. Both groups had comparatively high incidences of adverse events (AEs) but the difference was not significant between the two arms. However, the AEs of the skin and endocrine system in the combination immunotherapy arm were significantly higher than those of the sunitinib arm, while the AEs of the blood system were significantly lower than those of the sunitinib arm. (3) No matter the expression of PD-L1 in RCC patients was negative or positive (1% as the Cut-off value), the OS and PFS of patients treated with combination immunotherapy were higher than those treated with sunitinib. Conclusion: Combined immunotherapy can significantly prolong the OS and PFS of patients with advanced RCC, but the incidence of AEs in different systems is different, and the expression of PD-L1 in RCC patients (with 1% as the Cut-off value) does not affect the benefit of combination immunotherapy.
Objective: To systematically evaluate the safety and efficacy of PD-1/PD-L1 inhibitor-based immunotherapy (hereinafter referred to as "combination immunotherapy") compared with sunitinib in the treatment of advanced renal cell carcinoma (RCC). Methods: Databases such as PubMed, Embase, Cochrane Library, and CNKI were searched from the date of their establishment to October 2022 to collect the randomized controlled trials (RCTs) of combination immunotherapy versus sunitinib for the treatment of advanced renal cell carcinoma (RCC).Two reviewers independently evaluated the quality of included studies, extracted data, and cross-checked the information. Meta-analysis was performed using StataMP16.0 software. Results: A total of 6 RCTs were included. The results of the Meta-analysis showed that: (1)Effectiveness. Compared to sunitinib, combination immunotherapy significantly improved overall survival (HR=0.74, 95% CI [0.67, 0.80], P<0.01) and progression-free survival (HR=0.66, 95% CI [0.51, 0.81], P<0.01) in patients with advanced RCC. (2) Safety. Both groups had comparatively high incidences of adverse events (AEs) but the difference was not significant between the two arms. However, the AEs of the skin and endocrine system in the combination immunotherapy arm were significantly higher than those of the sunitinib arm, while the AEs of the blood system were significantly lower than those of the sunitinib arm. (3) No matter the expression of PD-L1 in RCC patients was negative or positive (1% as the Cut-off value), the OS and PFS of patients treated with combination immunotherapy were higher than those treated with sunitinib. Conclusion: Combined immunotherapy can significantly prolong the OS and PFS of patients with advanced RCC, but the incidence of AEs in different systems is different, and the expression of PD-L1 in RCC patients (with 1% as the Cut-off value) does not affect the benefit of combination immunotherapy.
2023, 30(5):401-411.
DOI: 10.3872/j.issn.1007-385X.2023.05.006
Abstract:
Objective：：To investigate the expression of peptidase M20 domain 1 (PM20D1) in human diffuse large B-cell lymphoma (DLBCL) cells and its relationship with hypoxia and prognosis. Methods: The effects of PM20D1 expression on proliferation,migration and apoptosis of DLBCL cells and its relationship with patients' prognosis were analyzed through GDC, TCGA and GTEx public databases. The enrichment analysis of patients in different groups and the correlation analysis between PM20D1 and CD274 were used to validate whether PM20D1 was the hypoxia-related gene of DLBCL. ChEA, ENCODE and hTFtarget databases were used to analyze the transcription factors (TFs) and miRNAs that upstream regulate PM20D1 expression and the relationship between differential expression of PM20D1 and chemotherapeutic drug sensitivity. The expression level of PM20D1 in normal lymphocytes and DLBCL cells was detected by WB method, the target gene was reduced by the siRNA sequence of PM20D1, and the knockdown efficiency of PM20D1 in SUDHL2 and SUDHL10 cells was verified by qPCR and WB methods.The effect of PM20D1 on cell proliferation and migration ability after knockdown was detected by CCK-8 method and Transwell assays, respectively, and the apoptosis level was detected by flow cytometry. Results: PM20D1 was highly expressed in DLBCL tissues and was correlated with a poor prognosis (P<0.05 or P<0.01).Enrichment analysis showed that the PM20D1 high expression group and high ssGSEA score group were mainly involved in cellular electrocoupling communication, triglyceride metabolism process regulation and cytoplasmic translation initiation complex process, and PM20D1 expression was positively correlated with CD274 expression at immune checkpoint (P<0.01, r=0.757). After knocking down PM20D1 in SUDHL2 and SUDHL10 cells, the proliferation and migration of cells decreased significantly (all P<0.05), and apoptosis increased significantly (P<0.05). Conclusion: PM20D1 gene was highly expressed in DLBCL tissues and cells, and in closely related to patient prognosis. PM20D1 may promote the occurrence and development of DLBCL by promoting the proliferation, migration and inhibiting the apoptosis of DLBCL cells.
Objective：：To investigate the expression of peptidase M20 domain 1 (PM20D1) in human diffuse large B-cell lymphoma (DLBCL) cells and its relationship with hypoxia and prognosis. Methods: The effects of PM20D1 expression on proliferation,migration and apoptosis of DLBCL cells and its relationship with patients' prognosis were analyzed through GDC, TCGA and GTEx public databases. The enrichment analysis of patients in different groups and the correlation analysis between PM20D1 and CD274 were used to validate whether PM20D1 was the hypoxia-related gene of DLBCL. ChEA, ENCODE and hTFtarget databases were used to analyze the transcription factors (TFs) and miRNAs that upstream regulate PM20D1 expression and the relationship between differential expression of PM20D1 and chemotherapeutic drug sensitivity. The expression level of PM20D1 in normal lymphocytes and DLBCL cells was detected by WB method, the target gene was reduced by the siRNA sequence of PM20D1, and the knockdown efficiency of PM20D1 in SUDHL2 and SUDHL10 cells was verified by qPCR and WB methods.The effect of PM20D1 on cell proliferation and migration ability after knockdown was detected by CCK-8 method and Transwell assays, respectively, and the apoptosis level was detected by flow cytometry. Results: PM20D1 was highly expressed in DLBCL tissues and was correlated with a poor prognosis (P<0.05 or P<0.01).Enrichment analysis showed that the PM20D1 high expression group and high ssGSEA score group were mainly involved in cellular electrocoupling communication, triglyceride metabolism process regulation and cytoplasmic translation initiation complex process, and PM20D1 expression was positively correlated with CD274 expression at immune checkpoint (P<0.01, r=0.757). After knocking down PM20D1 in SUDHL2 and SUDHL10 cells, the proliferation and migration of cells decreased significantly (all P<0.05), and apoptosis increased significantly (P<0.05). Conclusion: PM20D1 gene was highly expressed in DLBCL tissues and cells, and in closely related to patient prognosis. PM20D1 may promote the occurrence and development of DLBCL by promoting the proliferation, migration and inhibiting the apoptosis of DLBCL cells.
2023, 30(5):412-423.
DOI: 10.3872/j.issn.1007-385X.2023.05.007
Abstract:
Objective: To screen the genes related to pyroptosis in colon cancer (CC) tissues by bioinformatics approach and to explore their relationship with patient prognosis to provide new therapeutic targets for CC patients. Methods: Gene expression, transcriptional data and clinical data of CC patients were downloaded from TCGA database and GEO database, respectively. R software was used to extract the expression of pyroptosis-related genes in TCGA transcription data, and the differentially expressed genes (DEGs) were screened out to construct a protein interaction network of the DEGs. The genes were typed by univariate analysis and cluster analysis, and the survival differences between the two subtypes were compared to obtain prognosis-related genes. Then, through Lasso regression analysis, cross-validation and optimization, the gene coefficients (Coef) were obtained to construct a prognosis prediction model for CC. The median risk score of the TCGA samples was calculated according to the prediction model, and the samples were divided into high-and-low risk groups. The GEO samples were used as the validation group, and survival analysis (Kaplan-Meier analysis), ROC curve, risk curve, PCA, and t-SNE analysis were performed on TCGA and GEO samples, respectively. Combined with the risk scores in the model, univariate and multivariate analyses were conducted to find the independent prognostic factors for colon cancer patients. The GO and KEGG analyses were then performed for the high-and-low risk groups. Finally, by ssGSEA analysis, immune cells and immune-related functions were scored for each sample to obtain the difference in immune cells and immune cell-related functions between the high-and-low risk groups. Results: A total of 52 pyroptosis genes were identified in colon cancer and normal colon tissues, and 40 DEGs were selected. A prognostic risk prediction model for colon cancer based on 15 genes was constructed by Cox regression and Lasso regression analysis, and the colon cancer patients were divided into high-and-low risk groups, with significant differences in survival between the two groups (P<0.001). The risk score of TCGA samples was calculated according to the prediction model, and the obtained median risk score was verified using the GEO database, which showed a significant difference in survival between high-and-low risk groups (P=0.013). The risk score calculated by the prediction model was found to be an independent prognostic factor for predicting the survival of colon cancer patients. The GO enrichment analysis, KEGG enrichment analysis, and ssGSEA analysis of the DEGs showed a significant reduction in immune cell infiltration in the high-risk group of patients. Conclusion: A prognostic risk prediction model for colon cancer patients based on 15 genes by a bioinformatic approach was constructed. These genes also play an important role in colon cancer immunity.
Objective: To screen the genes related to pyroptosis in colon cancer (CC) tissues by bioinformatics approach and to explore their relationship with patient prognosis to provide new therapeutic targets for CC patients. Methods: Gene expression, transcriptional data and clinical data of CC patients were downloaded from TCGA database and GEO database, respectively. R software was used to extract the expression of pyroptosis-related genes in TCGA transcription data, and the differentially expressed genes (DEGs) were screened out to construct a protein interaction network of the DEGs. The genes were typed by univariate analysis and cluster analysis, and the survival differences between the two subtypes were compared to obtain prognosis-related genes. Then, through Lasso regression analysis, cross-validation and optimization, the gene coefficients (Coef) were obtained to construct a prognosis prediction model for CC. The median risk score of the TCGA samples was calculated according to the prediction model, and the samples were divided into high-and-low risk groups. The GEO samples were used as the validation group, and survival analysis (Kaplan-Meier analysis), ROC curve, risk curve, PCA, and t-SNE analysis were performed on TCGA and GEO samples, respectively. Combined with the risk scores in the model, univariate and multivariate analyses were conducted to find the independent prognostic factors for colon cancer patients. The GO and KEGG analyses were then performed for the high-and-low risk groups. Finally, by ssGSEA analysis, immune cells and immune-related functions were scored for each sample to obtain the difference in immune cells and immune cell-related functions between the high-and-low risk groups. Results: A total of 52 pyroptosis genes were identified in colon cancer and normal colon tissues, and 40 DEGs were selected. A prognostic risk prediction model for colon cancer based on 15 genes was constructed by Cox regression and Lasso regression analysis, and the colon cancer patients were divided into high-and-low risk groups, with significant differences in survival between the two groups (P<0.001). The risk score of TCGA samples was calculated according to the prediction model, and the obtained median risk score was verified using the GEO database, which showed a significant difference in survival between high-and-low risk groups (P=0.013). The risk score calculated by the prediction model was found to be an independent prognostic factor for predicting the survival of colon cancer patients. The GO enrichment analysis, KEGG enrichment analysis, and ssGSEA analysis of the DEGs showed a significant reduction in immune cell infiltration in the high-risk group of patients. Conclusion: A prognostic risk prediction model for colon cancer patients based on 15 genes by a bioinformatic approach was constructed. These genes also play an important role in colon cancer immunity.
8 Research progress of tumor immune microenvironment classification-based immunotherapeutic strategies
2023, 30(5):424-431.
DOI: 10.3872/j.issn.1007-385X.2023.05.008
Abstract:
肿瘤免疫微环境（TIME）是肿瘤细胞得以生存和发展的复杂环境，其组成成分及相关特征在调节肿瘤的发生和发展中发挥重要作用，并影响不同免疫疗法的临床疗效。TIME的研究为实体瘤诊疗开辟了一条新的路径，因此针对TIME的治疗策略具有发展前景且成为探索方向，以帮助指导和改善实体瘤的治疗。本文基于FOWLER团队确认的TIME四分型理论，进一步阐述不同分型的TIME特征及潜在可适用的免疫治疗方式，对目前基于TIME分型的肿瘤免疫治疗选择提供指导。同时提出在成像引导的测序等新技术协助下，新的生物标志物、TIME分型理论和治疗靶点的涌现，为实体瘤免疫疗法赋予光明前景。在新的疗法不断出现的同时，基于TIME的免疫治疗研究方向仍应尽可能提前关口，以实现肿瘤早诊早治的目的。
肿瘤免疫微环境（TIME）是肿瘤细胞得以生存和发展的复杂环境，其组成成分及相关特征在调节肿瘤的发生和发展中发挥重要作用，并影响不同免疫疗法的临床疗效。TIME的研究为实体瘤诊疗开辟了一条新的路径，因此针对TIME的治疗策略具有发展前景且成为探索方向，以帮助指导和改善实体瘤的治疗。本文基于FOWLER团队确认的TIME四分型理论，进一步阐述不同分型的TIME特征及潜在可适用的免疫治疗方式，对目前基于TIME分型的肿瘤免疫治疗选择提供指导。同时提出在成像引导的测序等新技术协助下，新的生物标志物、TIME分型理论和治疗靶点的涌现，为实体瘤免疫疗法赋予光明前景。在新的疗法不断出现的同时，基于TIME的免疫治疗研究方向仍应尽可能提前关口，以实现肿瘤早诊早治的目的。
2023, 30(5):432-437.
DOI: 10.3872/j.issn.1007-385X.2023.05.009
Abstract:
随着细胞代谢相关研究的不断深入，代谢重编程已被证实是恶性肿瘤的重要标志之一，其主要方式包括糖酵解、氧化磷酸化、氨基酸代谢、脂肪酸代谢和核苷酸代谢等。代谢重编程中的氧化磷酸化、糖酵解等为恶性肿瘤细胞生长提供了能量基础；糖酵解及脂质代谢过程的变化会影响恶性肿瘤细胞的侵袭及转移；而糖酵解途径对恶性肿瘤的耐药性有影响。因此，代谢重编程可以调控恶性肿瘤细胞的生长、转移等生物学行为，从而影响肿瘤的发展和治疗效果，是影响癌症发生和恶化的重要因素之一。目前，人们对肿瘤生物学复杂性的理解逐渐深入，这为基于代谢重编程研制肿瘤治疗药物提供了新的线索和思路。本文基于近年来关于恶性肿瘤代谢重编程的研究进展进行综述，介绍代谢重编程影响肿瘤生长、增殖和转移的潜在机制，讨论代谢重编程在肿瘤发生及靶向治疗中的意义，以期为癌症治疗提供更新颖更全面的见解和治疗策略。
随着细胞代谢相关研究的不断深入，代谢重编程已被证实是恶性肿瘤的重要标志之一，其主要方式包括糖酵解、氧化磷酸化、氨基酸代谢、脂肪酸代谢和核苷酸代谢等。代谢重编程中的氧化磷酸化、糖酵解等为恶性肿瘤细胞生长提供了能量基础；糖酵解及脂质代谢过程的变化会影响恶性肿瘤细胞的侵袭及转移；而糖酵解途径对恶性肿瘤的耐药性有影响。因此，代谢重编程可以调控恶性肿瘤细胞的生长、转移等生物学行为，从而影响肿瘤的发展和治疗效果，是影响癌症发生和恶化的重要因素之一。目前，人们对肿瘤生物学复杂性的理解逐渐深入，这为基于代谢重编程研制肿瘤治疗药物提供了新的线索和思路。本文基于近年来关于恶性肿瘤代谢重编程的研究进展进行综述，介绍代谢重编程影响肿瘤生长、增殖和转移的潜在机制，讨论代谢重编程在肿瘤发生及靶向治疗中的意义，以期为癌症治疗提供更新颖更全面的见解和治疗策略。
10 Research progress on the function of microRNA in drug resistance and treatment of colorectal cancer
2023, 30(5):438-444.
DOI: 10.3872/j.issn.1007-385X.2023.05.010
Abstract:
非编码小RNA（miRNA）是一种内源性非编码RNA，其通过靶向调控mRNA的表达在多种恶性肿瘤化疗耐受过程中发挥重要作用。在中国，结直肠癌（CRC）是预后极差的恶性肿瘤之一，越来越多的研究结果显示，特定miRNA的异常表达与CRC化疗耐药密切相关。部分miRNA可以通过影响DNA损伤修复和细胞周期检查点，减少肿瘤细胞的死亡，增强CRC化疗耐药性。miRNA的异常表达还会影响干细胞活性，抑制细胞凋亡，以及减少药物对肿瘤细胞的杀伤作用，从而引起CRC化疗耐药。此外，上皮间质转化、细胞代谢和自噬等机制也参与其中。基于此，以miRNA为靶点治疗CRC耐药的策略频频被提出。目前，从miRNA角度逆转CRC耐药的策略主要分为上调抑癌miRNA或功能性抑制促癌miRNA。根据临床需要，还可对miRNA进行化学修饰或利用病毒、偶联体和纳米颗粒等载体开发靶向递送系统以达到精准治疗的目的，改善患者预后，但具体的治疗策略仍需进一步探索。
非编码小RNA（miRNA）是一种内源性非编码RNA，其通过靶向调控mRNA的表达在多种恶性肿瘤化疗耐受过程中发挥重要作用。在中国，结直肠癌（CRC）是预后极差的恶性肿瘤之一，越来越多的研究结果显示，特定miRNA的异常表达与CRC化疗耐药密切相关。部分miRNA可以通过影响DNA损伤修复和细胞周期检查点，减少肿瘤细胞的死亡，增强CRC化疗耐药性。miRNA的异常表达还会影响干细胞活性，抑制细胞凋亡，以及减少药物对肿瘤细胞的杀伤作用，从而引起CRC化疗耐药。此外，上皮间质转化、细胞代谢和自噬等机制也参与其中。基于此，以miRNA为靶点治疗CRC耐药的策略频频被提出。目前，从miRNA角度逆转CRC耐药的策略主要分为上调抑癌miRNA或功能性抑制促癌miRNA。根据临床需要，还可对miRNA进行化学修饰或利用病毒、偶联体和纳米颗粒等载体开发靶向递送系统以达到精准治疗的目的，改善患者预后，但具体的治疗策略仍需进一步探索。
2023, 30(5):445-450.
DOI: 10.3872/j.issn.1007-385X.2023.05.011
Abstract:
睾丸肿瘤好发于青少年和年轻男性，其中生殖细胞肿瘤是最常见的睾丸肿瘤。目前普遍认为睾丸生殖细胞肿瘤是由生精小管内生殖细胞癌前病变发展而来，生殖细胞癌前病变在机体青春期后可进一步发展为侵袭性的睾丸生殖细胞肿瘤，包括精原细胞瘤和非精原细胞瘤。近年来，男性睾丸生殖细胞肿瘤发病率逐渐增加，睾丸生殖细胞肿瘤具有高度遗传易感性和多基因遗传特性，基因突变及其所介导的信号通路和miRNA 的调控均可影响其发生发展与治疗敏感性。因此靶向突变基因或参与调控的miRNA 可作为潜在的治疗靶点并为针对性生物治疗的研究拓展方向，除此之外，睾丸生殖细胞肿瘤还具有抗原特异性，一些针对睾丸生殖细胞肿瘤特点开发而来的肿瘤疫苗以及生物治疗和常规治疗联合使用的治疗方式都得到了长足的发展，具备十分广阔的前景。
睾丸肿瘤好发于青少年和年轻男性，其中生殖细胞肿瘤是最常见的睾丸肿瘤。目前普遍认为睾丸生殖细胞肿瘤是由生精小管内生殖细胞癌前病变发展而来，生殖细胞癌前病变在机体青春期后可进一步发展为侵袭性的睾丸生殖细胞肿瘤，包括精原细胞瘤和非精原细胞瘤。近年来，男性睾丸生殖细胞肿瘤发病率逐渐增加，睾丸生殖细胞肿瘤具有高度遗传易感性和多基因遗传特性，基因突变及其所介导的信号通路和miRNA 的调控均可影响其发生发展与治疗敏感性。因此靶向突变基因或参与调控的miRNA 可作为潜在的治疗靶点并为针对性生物治疗的研究拓展方向，除此之外，睾丸生殖细胞肿瘤还具有抗原特异性，一些针对睾丸生殖细胞肿瘤特点开发而来的肿瘤疫苗以及生物治疗和常规治疗联合使用的治疗方式都得到了长足的发展，具备十分广阔的前景。
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
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Supported by:Beijing E-Tiller Technology Development Co., Ltd.