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CD73⁺CD8⁺ T细胞定义了弥漫性大B细胞淋巴瘤(DLBCL)患者中具有抗肿瘤潜力的一个亚群。

CD73CD8 T cells define a subset with anti-tumor potential in DLBCL patients.

作者信息

Zhang Lingyu, Cheng Rui, Fan Zongbing, Liu Yunxiao, Huang Jie, Peng Jiabing

机构信息

Department of Pharmacy, The Fuyang Hospital of Anhui Medical University, Fuyang, Anhui, China.

出版信息

Front Med (Lausanne). 2025 May 2;12:1526772. doi: 10.3389/fmed.2025.1526772. eCollection 2025.

Abstract

INTRODUCTION

CD73, a recently discovered immune checkpoint, catalyzes the conversion of AMP to adenosine, thereby suppressing anti-tumor immune responses.CD8 T cells play a critical role in the immune response against cancer, yet their functionality can be modulated by various factors within the tumor microenvironment. In this study, we focus on identifying and characterizing CD73CD8 T cells in the peripheral blood of patients with diffuse large B-cell lymphoma (DLBCL), aiming to elucidate their functional and phenotypic roles in tumor immunity.

METHODS

Using flow cytometry, we analyzed the expression of inhibitory receptors (e.g., PD-1, TIM-3) and activating markers (e.g., CD25, CD69) on CD73CD8 T cells compared to CD73CD8 T cells. functional assays were conducted to assess their cytotoxic activity against tumor cells, including cytokine production and tumor cell killing capacity.

RESULTS

CD73CD8 T cells exhibited a distinct immunophenotypic profile, characterized by reduced expression of inhibitory receptors and enhanced cytotoxic activity compared to their CD73 counterparts. These cells demonstrated higher levels of effector molecules (e.g., IFN-γ, TNF-α) and lower exhausted markers. The findings suggest that CD73CD8 T cells may retain stronger anti-tumor potential.

DISCUSSION

This study highlights CD73CD8 T cells as a unique functional subset with potential therapeutic relevance in DLBCL. Their reduced exhaustion and heightened cytotoxicity position them as promising targets for immunotherapy strategies. However, the dual role of CD73 in adenosine-mediated immunosuppression warrants further investigation to reconcile its pro-tumorigenic effects with the observed anti-tumor activity of CD73CD8 T cells. Our findings deepen the understanding of CD8 T cell heterogeneity in DLBCL and emphasize the need for mechanistic studies to explore CD73's context-dependent functions.

摘要

引言

CD73是一种最近发现的免疫检查点,可催化AMP转化为腺苷,从而抑制抗肿瘤免疫反应。CD8 T细胞在抗癌免疫反应中起关键作用,但其功能可受到肿瘤微环境中各种因素的调节。在本研究中,我们着重于鉴定和表征弥漫性大B细胞淋巴瘤(DLBCL)患者外周血中的CD73⁺CD8 T细胞,旨在阐明它们在肿瘤免疫中的功能和表型作用。

方法

我们使用流式细胞术分析了CD73⁺CD8 T细胞与CD73⁻CD8 T细胞相比,抑制性受体(如PD-1、TIM-3)和活化标志物(如CD25、CD69)的表达情况。进行了功能测定以评估它们对肿瘤细胞的细胞毒性活性,包括细胞因子产生和肿瘤细胞杀伤能力。

结果

与CD73⁻对应细胞相比,CD73⁺CD8 T细胞表现出独特的免疫表型特征,其特征在于抑制性受体表达降低和细胞毒性活性增强。这些细胞显示出更高水平的效应分子(如IFN-γ、TNF-α)和更低的耗竭标志物。研究结果表明,CD73⁺CD8 T细胞可能保留更强的抗肿瘤潜力。

讨论

本研究强调CD73⁺CD8 T细胞是DLBCL中具有潜在治疗相关性的独特功能亚群。它们较低的耗竭程度和增强的细胞毒性使其成为免疫治疗策略的有希望的靶点。然而,CD73在腺苷介导的免疫抑制中的双重作用值得进一步研究,以协调其促肿瘤作用与观察到的CD73⁺CD8 T细胞的抗肿瘤活性。我们的研究结果加深了对DLBCL中CD8 T细胞异质性的理解,并强调需要进行机制研究以探索CD73的背景依赖性功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09fb/12081347/238acd5e665d/fmed-12-1526772-g001.jpg

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