T-cell dysfunction in natural killer/T-cell lymphoma
Natural killer/T-cell lymphoma (NKTCL) is an incurable aggressive T-cell lymphoma closely correlated with Epstein‒Barr virus (EBV) infection. Chronic and consistent viral infection induces T-cell exhaustion. Herein, we describe T-cell dysfunction in NKTCL patients for the first time. Peripheral bloo...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2212532 |
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| author | Xiaoyan Feng Miaomiao Meng Hongwen Li Yuyang Gao Wenting Song Ruiqing Di Zhaoming Li Xudong Zhang Mingzhi Zhang |
| author_facet | Xiaoyan Feng Miaomiao Meng Hongwen Li Yuyang Gao Wenting Song Ruiqing Di Zhaoming Li Xudong Zhang Mingzhi Zhang |
| author_sort | Xiaoyan Feng |
| collection | DOAJ |
| description | Natural killer/T-cell lymphoma (NKTCL) is an incurable aggressive T-cell lymphoma closely correlated with Epstein‒Barr virus (EBV) infection. Chronic and consistent viral infection induces T-cell exhaustion. Herein, we describe T-cell dysfunction in NKTCL patients for the first time. Peripheral blood mononuclear cells (PBMCs) from age-matched healthy donors (HDs) and NKTCL patients were collected, and lymphocyte distributions, multiple surface inhibitory receptors (IRs), effector cytokine production and cell proliferation were determined by flow cytometry. PBMCs from HDs were cocultured with NKTCL cell lines to verify the clinical findings. IR expression was further assessed in NKTCL tumor biopsies using multiplex immunohistochemistry (mIHC). NKTCL patients have higher frequencies than HDs of inhibitory T regulatory cells (Tregs) and myeloid-derived suppressor cells (MDSCs). T-cell distribution also varies between NKTCL patients and HDs. T cells from NKTCL patients demonstrated higher expression levels of multiple IRs than HDs. Meanwhile, T-cell proliferation and interferon-γ production was significantly reduced in NKTCL patients. More importantly, the number of EBV-specific cytotoxic cells was lower in NTKCL patients, and these cells demonstrated upregulation of multiple IRs and secreted fewer effector cytokines. Interestingly, NKTCL cells caused normal PBMCs to acquire T-cell exhaustion phenotypes and induced generation of Tregs and MDSCs. In line with ex vivo finding, mIHC results showed that CD8+ T cells from NKTCL tumor biopsies expressed much higher level of IRs compared with reactive lymphoid hyperplasia individuals. The immune microenvironment of NKTCL patients exhibited T-cell dysfunction and accumulation of inhibitory cell components, which may contribute to impaired antitumor immunity. |
| format | Article |
| id | doaj-art-e35c6cd512d74a9bb5a9889cdc7fe579 |
| institution | Kabale University |
| issn | 2162-402X |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-e35c6cd512d74a9bb5a9889cdc7fe5792024-12-27T17:34:38ZengTaylor & Francis GroupOncoImmunology2162-402X2023-12-0112110.1080/2162402X.2023.2212532T-cell dysfunction in natural killer/T-cell lymphomaXiaoyan Feng0Miaomiao Meng1Hongwen Li2Yuyang Gao3Wenting Song4Ruiqing Di5Zhaoming Li6Xudong Zhang7Mingzhi Zhang8Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaNatural killer/T-cell lymphoma (NKTCL) is an incurable aggressive T-cell lymphoma closely correlated with Epstein‒Barr virus (EBV) infection. Chronic and consistent viral infection induces T-cell exhaustion. Herein, we describe T-cell dysfunction in NKTCL patients for the first time. Peripheral blood mononuclear cells (PBMCs) from age-matched healthy donors (HDs) and NKTCL patients were collected, and lymphocyte distributions, multiple surface inhibitory receptors (IRs), effector cytokine production and cell proliferation were determined by flow cytometry. PBMCs from HDs were cocultured with NKTCL cell lines to verify the clinical findings. IR expression was further assessed in NKTCL tumor biopsies using multiplex immunohistochemistry (mIHC). NKTCL patients have higher frequencies than HDs of inhibitory T regulatory cells (Tregs) and myeloid-derived suppressor cells (MDSCs). T-cell distribution also varies between NKTCL patients and HDs. T cells from NKTCL patients demonstrated higher expression levels of multiple IRs than HDs. Meanwhile, T-cell proliferation and interferon-γ production was significantly reduced in NKTCL patients. More importantly, the number of EBV-specific cytotoxic cells was lower in NTKCL patients, and these cells demonstrated upregulation of multiple IRs and secreted fewer effector cytokines. Interestingly, NKTCL cells caused normal PBMCs to acquire T-cell exhaustion phenotypes and induced generation of Tregs and MDSCs. In line with ex vivo finding, mIHC results showed that CD8+ T cells from NKTCL tumor biopsies expressed much higher level of IRs compared with reactive lymphoid hyperplasia individuals. The immune microenvironment of NKTCL patients exhibited T-cell dysfunction and accumulation of inhibitory cell components, which may contribute to impaired antitumor immunity.https://www.tandfonline.com/doi/10.1080/2162402X.2023.2212532Epstein‒Barr virusinhibitory receptorsNK/T-cell lymphomaT-cell exhaustion |
| spellingShingle | Xiaoyan Feng Miaomiao Meng Hongwen Li Yuyang Gao Wenting Song Ruiqing Di Zhaoming Li Xudong Zhang Mingzhi Zhang T-cell dysfunction in natural killer/T-cell lymphoma OncoImmunology Epstein‒Barr virus inhibitory receptors NK/T-cell lymphoma T-cell exhaustion |
| title | T-cell dysfunction in natural killer/T-cell lymphoma |
| title_full | T-cell dysfunction in natural killer/T-cell lymphoma |
| title_fullStr | T-cell dysfunction in natural killer/T-cell lymphoma |
| title_full_unstemmed | T-cell dysfunction in natural killer/T-cell lymphoma |
| title_short | T-cell dysfunction in natural killer/T-cell lymphoma |
| title_sort | t cell dysfunction in natural killer t cell lymphoma |
| topic | Epstein‒Barr virus inhibitory receptors NK/T-cell lymphoma T-cell exhaustion |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2212532 |
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