T-cell dysfunction in natural killer/T-cell lymphoma.
T-cell dysfunction in natural killer/T-cell lymphoma.
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DOI：
10.1080/2162402x.2023.2212532
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发表时间：
2023
期刊：
影响因子：
7.2
通讯作者：
中科院分区：
文献类型：
--
作者：
自然杀伤/T细胞淋巴瘤(NKTCL)是一种与EB病毒(EBV)感染密切相关的不可治愈的侵袭性T细胞淋巴瘤。慢性持续的病毒感染会导致T细胞耗尽。在此，我们首次描述了NKTCL患者的T细胞功能障碍。采集年龄匹配的健康献血者和NKTCL患者外周血单个核细胞(PBMC)，用流式细胞仪检测淋巴细胞分布、多表面抑制受体(IRS)、效应细胞因子产生和细胞增殖。将人外周血单个核细胞与NKTCL细胞共培养，以验证其临床表现。用多重免疫组织化学(MIHC)进一步检测NKTCL肿瘤活检组织中IR的表达。NKTCL患者抑制性T调节细胞(Tregs)和髓系来源抑制细胞(MDSCs)的频率高于HD。T细胞在NKTCL患者和HD患者中的分布也不同。NKTCL患者的T细胞表达多重IR的水平高于HD。同时，NKTCL患者的T细胞增殖和干扰素-γ的产生显著降低。更重要的是，在NTKCL患者中，EBV特异性细胞毒细胞数量较少，这些细胞表现为多个IR上调，分泌较少的效应细胞因子。有趣的是，NKTCL细胞导致正常PBMC获得T细胞耗竭表型，并诱导产生Tregs和MDSCs。与体外研究结果一致，mIHC结果显示，NKTCL肿瘤活检组织中的CD8+T细胞比反应性淋巴组织增生症患者表达更高水平的IRS。NKTCL患者的免疫微环境表现为T细胞功能障碍和抑制性细胞成分积聚，这可能是NKTCL患者抗肿瘤免疫受损的原因之一。
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.
影响因子：
3.7
作者：
Li J;Zeng XH;Mo HY;Rolén U;Gao YF;Zhang XS;Chen QY;Zhang L;Zeng MS;Li MZ;Huang WL;Wang XN;Zeng YX;Masucci MG
通讯作者：
Masucci MG