Exhausted CD8+T Cells in the Tumor Immune Microenvironment: New Pathways to Therapy
Tumor-specific CD8+T cells are exposed to persistent antigenic stimulation which induces a dysfunctional state called “exhaustion.” Though functioning to limit damage caused by immune response, T cell exhaustion leads to attenuated effector function whereby cytotoxic CD8+T cells fail to control tumo...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2020.622509/full |
| _version_ | 1819174193101537280 |
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| author | Weiqin Jiang Yinjun He Wenguang He Guosheng Wu Xile Zhou Qinsong Sheng Weixiang Zhong Yimin Lu Yongfeng Ding Qi Lu Feng Ye Hanju Hua |
| author_facet | Weiqin Jiang Yinjun He Wenguang He Guosheng Wu Xile Zhou Qinsong Sheng Weixiang Zhong Yimin Lu Yongfeng Ding Qi Lu Feng Ye Hanju Hua |
| author_sort | Weiqin Jiang |
| collection | DOAJ |
| description | Tumor-specific CD8+T cells are exposed to persistent antigenic stimulation which induces a dysfunctional state called “exhaustion.” Though functioning to limit damage caused by immune response, T cell exhaustion leads to attenuated effector function whereby cytotoxic CD8+T cells fail to control tumor progression in the late stage. This pathway is a dynamic process from activation to “progenitor exhaustion” through to “terminally exhaustion” with distinct properties. With the rapid development of immunotherapy via enhancing T cell function, new studies are dissecting the mechanisms and identifying specific biomarkers of dynamic differentiation during the process of exhaustion. Further, although immune checkpoint inhibitors (ICIs) have achieved great success in clinical practice, most patients still show limited efficacy to ICIs. The expansion and differentiation of progenitor exhausted T cells explained the success of ICIs while the depletion of the progenitor T cell pool and the transient effector function of terminally exhausted T cells accounted for the failure of immune monotherapy in the context of exorbitant tumor burden. Thus, combination strategies are urgent to be utilized based on the reduction of tumor burden or the expansion of the progenitor T cell pool. In this review, we aim to introduce the concept of homeostasis of the activated and exhausted status of CD8+T cells in the tumor immune microenvironment, and present recent findings on dynamic differentiation process during T cell exhaustion and the implications for combination strategies in immune therapy. |
| first_indexed | 2024-12-22T20:35:05Z |
| format | Article |
| id | doaj.art-b9eef6fa27524d06af123e637369daac |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-22T20:35:05Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-b9eef6fa27524d06af123e637369daac2022-12-21T18:13:29ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-02-011110.3389/fimmu.2020.622509622509Exhausted CD8+T Cells in the Tumor Immune Microenvironment: New Pathways to TherapyWeiqin Jiang0Yinjun He1Wenguang He2Guosheng Wu3Xile Zhou4Qinsong Sheng5Weixiang Zhong6Yimin Lu7Yongfeng Ding8Qi Lu9Feng Ye10Hanju Hua11Department of Colorectal Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, ChinaDepartment of Colorectal Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, ChinaDepartment of Radiology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Colorectal Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, ChinaDepartment of Colorectal Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, ChinaDepartment of Colorectal Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, ChinaDepartment of Pathology, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Surgical Oncology, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Medical Oncology, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, ChinaCollege of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Colorectal Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, ChinaDepartment of Colorectal Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, ChinaTumor-specific CD8+T cells are exposed to persistent antigenic stimulation which induces a dysfunctional state called “exhaustion.” Though functioning to limit damage caused by immune response, T cell exhaustion leads to attenuated effector function whereby cytotoxic CD8+T cells fail to control tumor progression in the late stage. This pathway is a dynamic process from activation to “progenitor exhaustion” through to “terminally exhaustion” with distinct properties. With the rapid development of immunotherapy via enhancing T cell function, new studies are dissecting the mechanisms and identifying specific biomarkers of dynamic differentiation during the process of exhaustion. Further, although immune checkpoint inhibitors (ICIs) have achieved great success in clinical practice, most patients still show limited efficacy to ICIs. The expansion and differentiation of progenitor exhausted T cells explained the success of ICIs while the depletion of the progenitor T cell pool and the transient effector function of terminally exhausted T cells accounted for the failure of immune monotherapy in the context of exorbitant tumor burden. Thus, combination strategies are urgent to be utilized based on the reduction of tumor burden or the expansion of the progenitor T cell pool. In this review, we aim to introduce the concept of homeostasis of the activated and exhausted status of CD8+T cells in the tumor immune microenvironment, and present recent findings on dynamic differentiation process during T cell exhaustion and the implications for combination strategies in immune therapy.https://www.frontiersin.org/articles/10.3389/fimmu.2020.622509/fullCD8+ T cell exhaustionCD8+ T cell activationdifferentiationimmunotherapytumor microenvironment |
| spellingShingle | Weiqin Jiang Yinjun He Wenguang He Guosheng Wu Xile Zhou Qinsong Sheng Weixiang Zhong Yimin Lu Yongfeng Ding Qi Lu Feng Ye Hanju Hua Exhausted CD8+T Cells in the Tumor Immune Microenvironment: New Pathways to Therapy Frontiers in Immunology CD8+ T cell exhaustion CD8+ T cell activation differentiation immunotherapy tumor microenvironment |
| title | Exhausted CD8+T Cells in the Tumor Immune Microenvironment: New Pathways to Therapy |
| title_full | Exhausted CD8+T Cells in the Tumor Immune Microenvironment: New Pathways to Therapy |
| title_fullStr | Exhausted CD8+T Cells in the Tumor Immune Microenvironment: New Pathways to Therapy |
| title_full_unstemmed | Exhausted CD8+T Cells in the Tumor Immune Microenvironment: New Pathways to Therapy |
| title_short | Exhausted CD8+T Cells in the Tumor Immune Microenvironment: New Pathways to Therapy |
| title_sort | exhausted cd8 t cells in the tumor immune microenvironment new pathways to therapy |
| topic | CD8+ T cell exhaustion CD8+ T cell activation differentiation immunotherapy tumor microenvironment |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2020.622509/full |
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