High CD8+tumor-infiltrating lymphocytes indicate severe exhaustion and poor prognosis in angioimmunoblastic T-cell lymphoma

Frontiers in Immunology

Immunology

Yiming Yang¹  Xueqin Deng²  Wenyan Zhang²  Yunxia Ye²  Zihang Chen²  Weiping Liu²  Sha Zhao²  Qiqi Zhu³  Ningning Chao⁴ 

[1] Department of Pathology, North Sichuan Medical College, Affiliated Hospital of North Sichuan Medical College, Nanchong, China;Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, Nanchong, China;Department of Pathology, West China Hospital, Sichuan University, Chengdu, China;Department of Pathology, West China Hospital, Sichuan University, Chengdu, China;Department of Pathology, North Sichuan Medical College, Affiliated Hospital of North Sichuan Medical College, Nanchong, China;Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, China;

关键词: angioimmunoblastic T-cell lymphoma;    CD8 + tumor-infiltrating lymphocytes;    exhaustion;    immune checkpoint;    single-cell RNA sequencing;    prognosis;    therapy;   

DOI  :  10.3389/fimmu.2023.1228004

 received in 2023-05-24, accepted in 2023-08-23,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundExhaustion of CD8+ tumor-infiltrating lymphocytes (TILs), characterized by the overexpression of immune checkpoints (IC), is a major impediment to anti-tumor immunity. However, the exhaustion status of CD8+TILs in angioimmunoblastic T cell lymphoma (AITL) remains unclear. Therefore, we aimed to elucidate the exhaustion status of CD8+TILs in AITL and its influence on prognosis.MethodsThe correlation between CD8+TILs and IC expression in AITL was analyzed using single-cell RNA sequencing (n = 2), flow cytometry (n = 20), and RNA sequencing (n = 20). Biological changes related to CD8+TILs exhaustion at different cytotoxic T lymphocyte (CTL) levels (mean expression levels of CD8A, CD8B, GZMA, GZMB, and PRF1) in AITL were evaluated using RNA sequencing (n = 20) and further validated using the GEO dataset (n = 51). The impact of CD8 protein expression and CTL levels on patient prognosis was analyzed using flow cytometry and RNA sequencing, respectively.ResultsOur findings demonstrated that the higher the infiltration of CD8+TILs, the higher was the proportion of exhausted CD8+TILs characterized by the overexpression of multiple IC. This was accompanied by extensive exhaustion-related biological changes, which suggested severe exhaustion in CD8+TILs and may be one of the main reasons for the poor prognosis of patients with high CD8+TILs and CTL.ConclusionOur study comprehensively reveals the exhaustion status of CD8+TILs and their potential negative impact on AITL prognosis, which facilitates further mechanistic studies and is valuable for guiding immunotherapy strategies.

【 授权许可】

Unknown   
Copyright © 2023 Zhu, Yang, Deng, Chao, Chen, Ye, Zhang, Liu and Zhao