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T-cell dysfunction in natural killer/T-cell lymphoma.
Feng, Xiaoyan; Meng, Miaomiao; Li, Hongwen; Gao, Yuyang; Song, Wenting; Di, Ruiqing; Li, Zhaoming; Zhang, Xudong; Zhang, Mingzhi.
Afiliación
  • Feng X; Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
  • Meng M; Academy of Medical Sciences of Zhengzhou University, Zhengzhou, Henan, China.
  • Li H; Lymphoma Diagnosis and Treatment Centre of Henan Province, Zhengzhou, Henan, China.
  • Gao Y; Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
  • Song W; Academy of Medical Sciences of Zhengzhou University, Zhengzhou, Henan, China.
  • Di R; Lymphoma Diagnosis and Treatment Centre of Henan Province, Zhengzhou, Henan, China.
  • Li Z; Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
  • Zhang X; Lymphoma Diagnosis and Treatment Centre of Henan Province, Zhengzhou, Henan, China.
  • Zhang M; Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Oncoimmunology ; 12(1): 2212532, 2023.
Article en En | MEDLINE | ID: mdl-37250921
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por Virus de Epstein-Barr / Linfoma Extranodal de Células NK-T Límite: Humans Idioma: En Revista: Oncoimmunology Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por Virus de Epstein-Barr / Linfoma Extranodal de Células NK-T Límite: Humans Idioma: En Revista: Oncoimmunology Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos