Analysis of single‐cell RNAseq identifies transitional states of T cells associated with hepatocellular carcinoma
Abstract Background Exhausted T cells and regulatory T cells (Tregs) comprise diverse subsets of tumor immunosuppressive microenvironment that play key roles in tumor progress. Understanding subset diversity in T cells is a critical question for developing cancer immunotherapy. Methods A total of 23...
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Wiley
2020-07-01
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| Series: | Clinical and Translational Medicine |
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| Online Access: | https://doi.org/10.1002/ctm2.133 |
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| author | Yanying Yang Fangming Liu Weiren Liu Mingyue Ma Jie Gao Yan Lu Li‐Hao Huang Xiaoying Li Yinghong Shi Xiangdong Wang Duojiao Wu |
| author_facet | Yanying Yang Fangming Liu Weiren Liu Mingyue Ma Jie Gao Yan Lu Li‐Hao Huang Xiaoying Li Yinghong Shi Xiangdong Wang Duojiao Wu |
| author_sort | Yanying Yang |
| collection | DOAJ |
| description | Abstract Background Exhausted T cells and regulatory T cells (Tregs) comprise diverse subsets of tumor immunosuppressive microenvironment that play key roles in tumor progress. Understanding subset diversity in T cells is a critical question for developing cancer immunotherapy. Methods A total of 235 specimens from surgical resections of hepatocellular carcinoma (HCC) patients were examined for infiltration of exhausted T cell (Tex) in tumor and adjacent tissue. We conducted deep single‐cell targeted immune profiling on CD3+ cells collected from tumor tissues, adjacent normal tissues (ANTs) and peripheral blood of HCC patients. Total 10 cell clusters were identified with distinct distributions and characteristics. Results We observed transitional differentiation of exhausted CD8+T cells and Tregs increasingly enriched in tumor tissue. The accumulation and location of Tex were related to the differences in the long‐term clinical outcome of HCC. Furthermore, data of single‐cell RNA‐seq showed that (1) cells transforming from effector CD8+ T cells to exhausted CD8+ T cells simultaneously expressed upregulated effector molecules and inhibitory receptors, (2) indicated alteration of gene expression related to stress response and cell cycle at early exhaustion stage, and (3) immunosuppressive Treg had profound activation in comparison to resting Tregs. Conclusions T cell exhaustion is a progressive process, and the gene‐expression profiling displayed T cell exhaustion and anergy are different. Accordingly, it is possible that functional exhaustion is caused by the combination effects of passive defects and overactivation in stress response. The results help to understand the dynamic framework of T cells function in cancer which is important for designing rational cancer immunotherapies. |
| first_indexed | 2024-12-12T04:56:29Z |
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| institution | Directory Open Access Journal |
| issn | 2001-1326 |
| language | English |
| last_indexed | 2024-12-12T04:56:29Z |
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| series | Clinical and Translational Medicine |
| spelling | doaj.art-36b3898ceb0c4085aa30ffc3915089ea2022-12-22T00:37:21ZengWileyClinical and Translational Medicine2001-13262020-07-01103n/an/a10.1002/ctm2.133Analysis of single‐cell RNAseq identifies transitional states of T cells associated with hepatocellular carcinomaYanying Yang0Fangming Liu1Weiren Liu2Mingyue Ma3Jie Gao4Yan Lu5Li‐Hao Huang6Xiaoying Li7Yinghong Shi8Xiangdong Wang9Duojiao Wu10Department of Endocrinology and Metabolism Zhongshan Hospital Key Laboratory of Metabolism and Molecular Medicine the Ministry of Education Fudan University Shanghai ChinaInstitute of Clinical Science Zhongshan Hospital Fudan University Shanghai ChinaLiver Surgery Department of Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Endocrinology and Metabolism Zhongshan Hospital Key Laboratory of Metabolism and Molecular Medicine the Ministry of Education Fudan University Shanghai ChinaInstitute of Clinical Science Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Endocrinology and Metabolism Zhongshan Hospital Key Laboratory of Metabolism and Molecular Medicine the Ministry of Education Fudan University Shanghai ChinaDepartment of Pathology & Immunology Washington University School of Medicine Saint Louis MissouriDepartment of Endocrinology and Metabolism Zhongshan Hospital Key Laboratory of Metabolism and Molecular Medicine the Ministry of Education Fudan University Shanghai ChinaLiver Surgery Department of Zhongshan Hospital Fudan University Shanghai ChinaInstitute of Clinical Science Zhongshan Hospital Fudan University Shanghai ChinaInstitute of Clinical Science Zhongshan Hospital Fudan University Shanghai ChinaAbstract Background Exhausted T cells and regulatory T cells (Tregs) comprise diverse subsets of tumor immunosuppressive microenvironment that play key roles in tumor progress. Understanding subset diversity in T cells is a critical question for developing cancer immunotherapy. Methods A total of 235 specimens from surgical resections of hepatocellular carcinoma (HCC) patients were examined for infiltration of exhausted T cell (Tex) in tumor and adjacent tissue. We conducted deep single‐cell targeted immune profiling on CD3+ cells collected from tumor tissues, adjacent normal tissues (ANTs) and peripheral blood of HCC patients. Total 10 cell clusters were identified with distinct distributions and characteristics. Results We observed transitional differentiation of exhausted CD8+T cells and Tregs increasingly enriched in tumor tissue. The accumulation and location of Tex were related to the differences in the long‐term clinical outcome of HCC. Furthermore, data of single‐cell RNA‐seq showed that (1) cells transforming from effector CD8+ T cells to exhausted CD8+ T cells simultaneously expressed upregulated effector molecules and inhibitory receptors, (2) indicated alteration of gene expression related to stress response and cell cycle at early exhaustion stage, and (3) immunosuppressive Treg had profound activation in comparison to resting Tregs. Conclusions T cell exhaustion is a progressive process, and the gene‐expression profiling displayed T cell exhaustion and anergy are different. Accordingly, it is possible that functional exhaustion is caused by the combination effects of passive defects and overactivation in stress response. The results help to understand the dynamic framework of T cells function in cancer which is important for designing rational cancer immunotherapies.https://doi.org/10.1002/ctm2.133CD8 T cellexhaustionhepatocellular carcinomaregulatory T cell |
| spellingShingle | Yanying Yang Fangming Liu Weiren Liu Mingyue Ma Jie Gao Yan Lu Li‐Hao Huang Xiaoying Li Yinghong Shi Xiangdong Wang Duojiao Wu Analysis of single‐cell RNAseq identifies transitional states of T cells associated with hepatocellular carcinoma Clinical and Translational Medicine CD8 T cell exhaustion hepatocellular carcinoma regulatory T cell |
| title | Analysis of single‐cell RNAseq identifies transitional states of T cells associated with hepatocellular carcinoma |
| title_full | Analysis of single‐cell RNAseq identifies transitional states of T cells associated with hepatocellular carcinoma |
| title_fullStr | Analysis of single‐cell RNAseq identifies transitional states of T cells associated with hepatocellular carcinoma |
| title_full_unstemmed | Analysis of single‐cell RNAseq identifies transitional states of T cells associated with hepatocellular carcinoma |
| title_short | Analysis of single‐cell RNAseq identifies transitional states of T cells associated with hepatocellular carcinoma |
| title_sort | analysis of single cell rnaseq identifies transitional states of t cells associated with hepatocellular carcinoma |
| topic | CD8 T cell exhaustion hepatocellular carcinoma regulatory T cell |
| url | https://doi.org/10.1002/ctm2.133 |
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