近年来,工程化T细胞治疗在肿瘤免疫治疗领域取得了重大进展。工程化T细胞治疗主要包括T细胞受体基因工程T细胞(T-cell receptor-engineered T cell,TCR-T)疗法和嵌合抗原受体T细胞(chimeric antigen receptor T cell,CAR-T)疗法,其中,CA...近年来,工程化T细胞治疗在肿瘤免疫治疗领域取得了重大进展。工程化T细胞治疗主要包括T细胞受体基因工程T细胞(T-cell receptor-engineered T cell,TCR-T)疗法和嵌合抗原受体T细胞(chimeric antigen receptor T cell,CAR-T)疗法,其中,CAR-T疗法在恶性血液肿瘤中展现出了巨大的潜力和应用价值,而TCR-T疗法则在部分实体瘤中呈现出了较好的治疗效果。然而,针对大部分肿瘤,特别是实体肿瘤,当前工程化T细胞疗法还存在效率低、安全性不足等问题。通过合成生物学手段使工程化T细胞克服当前限制,将为研制更安全、高效的工程化T细胞带来新的机遇。本文将从工程化T细胞的结构和信号激活、靶点选择、亲和力优化、安全性改造以及基因编辑改造等方面综述工程化T细胞的合成生物学改造策略,并探讨这些优化措施在肿瘤免疫治疗应用中的最新进展。展开更多
BACKGROUND Regulatory T cells(Tregs)and natural killer(NK)cells play an essential role in the development of bladder urothelial carcinoma(BUC).AIM To construct a prognosis-related model to judge the prognosis of patie...BACKGROUND Regulatory T cells(Tregs)and natural killer(NK)cells play an essential role in the development of bladder urothelial carcinoma(BUC).AIM To construct a prognosis-related model to judge the prognosis of patients with bladder cancer,meanwhile,predict the sensitivity of patients to chemotherapy and immunotherapy.METHODS Bladder cancer information data was obtained from The Cancer Genome Atlas and GSE32894.The CIBERSORT was used to calculate the immune score of each sample.Weighted gene co-expression network analysis was used to find genes that will have the same or similar expression patterns.Subsequently,multivariate cox regression and lasso regression was used to further screen prognosis-related genes.The prrophetic package was used to predict phenotype from gene expression data,drug sensitivity of external cell line and predict clinical data.RESULTS The stage and risk scores are independent prognostic factors in patients with BUC.Mutations in FGFR3 lead to an increase in Tregs percolation and affect the prognosis of the tumor,and additionally,EMP1,TCHH and CNTNAP3B in the model are mainly positively correlated with the expression of immune checkpoints,while CMTM8,SORT1 and IQSEC1 are negatively correlated with immune checkpoints and the high-risk group had higher sensitivity to chemotherapy drugs.CONCLUSION Prognosis-related models of bladder tumor patients,based on Treg and NK cell percolation in tumor tissue.In addition to judging the prognosis of patients with bladder cancer,it can also predict the sensitivity of patients to chemotherapy and immunotherapy.At the same time,patients were divided into high and low risk groups based on this model,and differences in genetic mutations were found between the high and low risk groups.展开更多
文摘近年来,工程化T细胞治疗在肿瘤免疫治疗领域取得了重大进展。工程化T细胞治疗主要包括T细胞受体基因工程T细胞(T-cell receptor-engineered T cell,TCR-T)疗法和嵌合抗原受体T细胞(chimeric antigen receptor T cell,CAR-T)疗法,其中,CAR-T疗法在恶性血液肿瘤中展现出了巨大的潜力和应用价值,而TCR-T疗法则在部分实体瘤中呈现出了较好的治疗效果。然而,针对大部分肿瘤,特别是实体肿瘤,当前工程化T细胞疗法还存在效率低、安全性不足等问题。通过合成生物学手段使工程化T细胞克服当前限制,将为研制更安全、高效的工程化T细胞带来新的机遇。本文将从工程化T细胞的结构和信号激活、靶点选择、亲和力优化、安全性改造以及基因编辑改造等方面综述工程化T细胞的合成生物学改造策略,并探讨这些优化措施在肿瘤免疫治疗应用中的最新进展。
文摘BACKGROUND Regulatory T cells(Tregs)and natural killer(NK)cells play an essential role in the development of bladder urothelial carcinoma(BUC).AIM To construct a prognosis-related model to judge the prognosis of patients with bladder cancer,meanwhile,predict the sensitivity of patients to chemotherapy and immunotherapy.METHODS Bladder cancer information data was obtained from The Cancer Genome Atlas and GSE32894.The CIBERSORT was used to calculate the immune score of each sample.Weighted gene co-expression network analysis was used to find genes that will have the same or similar expression patterns.Subsequently,multivariate cox regression and lasso regression was used to further screen prognosis-related genes.The prrophetic package was used to predict phenotype from gene expression data,drug sensitivity of external cell line and predict clinical data.RESULTS The stage and risk scores are independent prognostic factors in patients with BUC.Mutations in FGFR3 lead to an increase in Tregs percolation and affect the prognosis of the tumor,and additionally,EMP1,TCHH and CNTNAP3B in the model are mainly positively correlated with the expression of immune checkpoints,while CMTM8,SORT1 and IQSEC1 are negatively correlated with immune checkpoints and the high-risk group had higher sensitivity to chemotherapy drugs.CONCLUSION Prognosis-related models of bladder tumor patients,based on Treg and NK cell percolation in tumor tissue.In addition to judging the prognosis of patients with bladder cancer,it can also predict the sensitivity of patients to chemotherapy and immunotherapy.At the same time,patients were divided into high and low risk groups based on this model,and differences in genetic mutations were found between the high and low risk groups.
