Differential expression of inhibitory receptor NKG2A distinguishes disease‐specific exhausted CD8+ T cells
Abstract Exhausted CD8+ T (Tex) cells are caused by persistent antigenic stimulation during chronic viral infection or tumorigenesis. Tex cells upregulate and sustain the expressions of multiple immune inhibitory receptors (IRs). Blocking IRs of Tex cells, exemplified by PD‐1, can partially restore...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-03-01
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| Series: | MedComm |
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| Online Access: | https://doi.org/10.1002/mco2.111 |
| _version_ | 1818306978030551040 |
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| author | Xiangyu Chen Yao Lin Shuai Yue Yang Yang Xinxin Wang Zhiwei Pan Xiaofan Yang Leiqiong Gao Jing Zhou Zhirong Li Li Hu Jianfang Tang Qing Wu Yifei Wang Qin Tian Yaxing Hao Lifan Xu Bo Zhu Qizhao Huang Lilin Ye |
| author_facet | Xiangyu Chen Yao Lin Shuai Yue Yang Yang Xinxin Wang Zhiwei Pan Xiaofan Yang Leiqiong Gao Jing Zhou Zhirong Li Li Hu Jianfang Tang Qing Wu Yifei Wang Qin Tian Yaxing Hao Lifan Xu Bo Zhu Qizhao Huang Lilin Ye |
| author_sort | Xiangyu Chen |
| collection | DOAJ |
| description | Abstract Exhausted CD8+ T (Tex) cells are caused by persistent antigenic stimulation during chronic viral infection or tumorigenesis. Tex cells upregulate and sustain the expressions of multiple immune inhibitory receptors (IRs). Blocking IRs of Tex cells, exemplified by PD‐1, can partially restore their effector functions and thus lead to viral suppression or tumor remission. Tex cells derived from chronic viral infections share the expression spectrum of IRs with Tex cells derived from tumors; however, whether any IRs are selectively expressed by tumor‐derived Tex cells or virus‐derived Tex cells remains to be learnt. In the study, we found that Tex cells upregulate IR natural killer cell lectin‐like receptor isoform A (NKG2A) specifically in the context of tumor but not chronic viral infection. Moreover, the NKG2A expression is attributed to tumor antigen recognition and thus bias expressed by tumor‐specific Tex cells in the tumor microenvironment instead of their counterparts in the periphery. Such dichotomous NKG2A expression further dictates the differential responsiveness of Tex cells to NKG2A immune checkpoint blockade. Therefore, our study highlighted NKG2A as a disease‐dependent IR and provided novel insights into the distinct regulatory mechanisms underlying T cell exhaustion between tumor and chronic viral infection. |
| first_indexed | 2024-12-13T06:51:04Z |
| format | Article |
| id | doaj.art-38ed27414d70460a9581234169f86350 |
| institution | Directory Open Access Journal |
| issn | 2688-2663 |
| language | English |
| last_indexed | 2024-12-13T06:51:04Z |
| publishDate | 2022-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | MedComm |
| spelling | doaj.art-38ed27414d70460a9581234169f863502022-12-21T23:56:09ZengWileyMedComm2688-26632022-03-0131n/an/a10.1002/mco2.111Differential expression of inhibitory receptor NKG2A distinguishes disease‐specific exhausted CD8+ T cellsXiangyu Chen0Yao Lin1Shuai Yue2Yang Yang3Xinxin Wang4Zhiwei Pan5Xiaofan Yang6Leiqiong Gao7Jing Zhou8Zhirong Li9Li Hu10Jianfang Tang11Qing Wu12Yifei Wang13Qin Tian14Yaxing Hao15Lifan Xu16Bo Zhu17Qizhao Huang18Lilin Ye19School of Laboratory Medicine and Biotechnology Southern Medical University Guangzhou ChinaInstitute of Immunology Third Military Medical University Chongqing ChinaInstitute of Immunology Third Military Medical University Chongqing ChinaSchool of Laboratory Medicine and Biotechnology Southern Medical University Guangzhou ChinaInstitute of Cancer, Xinqiao Hospital Third Military Medical University Chongqing ChinaInstitute of Immunology Third Military Medical University Chongqing ChinaDermatology Hospital Southern Medical University Guangzhou ChinaInstitute of Immunology Third Military Medical University Chongqing ChinaInstitute of Immunology Third Military Medical University Chongqing ChinaInstitute of Immunology Third Military Medical University Chongqing ChinaInstitute of Immunology Third Military Medical University Chongqing ChinaInstitute of Immunology Third Military Medical University Chongqing ChinaInstitute of Immunology Third Military Medical University Chongqing ChinaSchool of Laboratory Medicine and Biotechnology Southern Medical University Guangzhou ChinaDermatology Hospital Southern Medical University Guangzhou ChinaInstitute of Immunology Third Military Medical University Chongqing ChinaInstitute of Immunology Third Military Medical University Chongqing ChinaInstitute of Cancer, Xinqiao Hospital Third Military Medical University Chongqing ChinaSchool of Laboratory Medicine and Biotechnology Southern Medical University Guangzhou ChinaSchool of Laboratory Medicine and Biotechnology Southern Medical University Guangzhou ChinaAbstract Exhausted CD8+ T (Tex) cells are caused by persistent antigenic stimulation during chronic viral infection or tumorigenesis. Tex cells upregulate and sustain the expressions of multiple immune inhibitory receptors (IRs). Blocking IRs of Tex cells, exemplified by PD‐1, can partially restore their effector functions and thus lead to viral suppression or tumor remission. Tex cells derived from chronic viral infections share the expression spectrum of IRs with Tex cells derived from tumors; however, whether any IRs are selectively expressed by tumor‐derived Tex cells or virus‐derived Tex cells remains to be learnt. In the study, we found that Tex cells upregulate IR natural killer cell lectin‐like receptor isoform A (NKG2A) specifically in the context of tumor but not chronic viral infection. Moreover, the NKG2A expression is attributed to tumor antigen recognition and thus bias expressed by tumor‐specific Tex cells in the tumor microenvironment instead of their counterparts in the periphery. Such dichotomous NKG2A expression further dictates the differential responsiveness of Tex cells to NKG2A immune checkpoint blockade. Therefore, our study highlighted NKG2A as a disease‐dependent IR and provided novel insights into the distinct regulatory mechanisms underlying T cell exhaustion between tumor and chronic viral infection.https://doi.org/10.1002/mco2.111cancer immunotherapychronic viral infectionNKG2AT cell exhaustion |
| spellingShingle | Xiangyu Chen Yao Lin Shuai Yue Yang Yang Xinxin Wang Zhiwei Pan Xiaofan Yang Leiqiong Gao Jing Zhou Zhirong Li Li Hu Jianfang Tang Qing Wu Yifei Wang Qin Tian Yaxing Hao Lifan Xu Bo Zhu Qizhao Huang Lilin Ye Differential expression of inhibitory receptor NKG2A distinguishes disease‐specific exhausted CD8+ T cells MedComm cancer immunotherapy chronic viral infection NKG2A T cell exhaustion |
| title | Differential expression of inhibitory receptor NKG2A distinguishes disease‐specific exhausted CD8+ T cells |
| title_full | Differential expression of inhibitory receptor NKG2A distinguishes disease‐specific exhausted CD8+ T cells |
| title_fullStr | Differential expression of inhibitory receptor NKG2A distinguishes disease‐specific exhausted CD8+ T cells |
| title_full_unstemmed | Differential expression of inhibitory receptor NKG2A distinguishes disease‐specific exhausted CD8+ T cells |
| title_short | Differential expression of inhibitory receptor NKG2A distinguishes disease‐specific exhausted CD8+ T cells |
| title_sort | differential expression of inhibitory receptor nkg2a distinguishes disease specific exhausted cd8 t cells |
| topic | cancer immunotherapy chronic viral infection NKG2A T cell exhaustion |
| url | https://doi.org/10.1002/mco2.111 |
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