Unraveling the interplay of CD8+T cells and microRNA signaling in cancer - implications for immune dysfunction and therapeutic approaches

Sep 21, 2026

MicroRNAs (miRNAs) act as key regulators of CD8+ T cell function in the complex tumor microenvironment (TME). This review synthesizes evidence across multiple cancer types to show how distinct miRNAs regulate CD8+ T cell activation, recruitment, infiltration, and effector performance. miRNA dysregulation promotes CD8+ T cell exhaustion and immune evasion, reducing antitumor immunity, while modulating miRNA expression may enhance CD8+ activity and improve immunotherapy outcomes. It also examines extracellular vesicles, cytokines, and the influence of radiotherapy and drugs on miRNA programs within the TME, highlighting miRNA targeting strategies for next-generation cancer immunotherapies.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages20

Reading Time50 min

AccessFree to download

Abstract

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Introduction

Zabeti Touchaei and Vahidi Journal of Translational Medicine (2024) 22:1131 [https://doi.org/10.1186/s12967-024-05963-5](https://doi.org/10.1186/s12967-024-05963-5) Journal of Translational Medicine REVIEW Open Access Unraveling the interplay of CD8 +T cells and microRNA signaling in cancer: implications for immune dysfunction and therapeutic approaches Arefeh Zabeti Touchaei1 and Sogand Vahidi2* Abstract MicroRNAs (miRNAs) emerge as critical regulators of CD8 + T cell function within the complex tumor microenvironment (TME) . This review explores the multifaceted interplay between miRNAs and CD8 + T cells across various cancers. We discuss how specific miRNAs influence CD8 + T cell activation, recruitment, infiltration, and effector function. Dysregulation of these miRNAs can contribute to CD8 + T cell exhaustion and immune evasion, hindering anti-tumor immunity. Conversely, manipulating miRNA expression holds promise for enhancing CD8 + T cell activity and improving cancer immunotherapy outcomes. We delve into the role of miRNAs in CD8 + T-cell function across different cancer types, including gliomas, gastric and colon cancer, oral squamous cell carcinoma, thyroid carcinoma, lymphomas, melanoma, breast cancer, renal cell carcinoma, ovarian cancer, uterine corpus endometrial cancer, bladder cancer, acute myeloid leukemia, chronic myelogenous leukemia, and osteosarcoma. Additionally, we explore how extracellular vesicles and cytokines modulate CD8 + T-cell function through complex interactions with miRNAs. Finally, we discuss the potential impact of radiotherapy and specific drugs on miRNA expression and CD8 + T-cell activity within the TME. This review highlights the immense potential of targeting miRNAs to manipulate CD8 + T-cell activity for the development of novel and improved cancer immunotherapies. Highlights – MiRNAs act as critical regulators of CD8+ T cell function within the tumor microenvironment (TME) . – Dysregulation of these miRNAs can lead to T cell exhaustion and immune evasion, compromising the body’s ability to fight cancer. – Manipulating miRNA expression offers a promising avenue for enhancing CD8+ T cell activity and improving cancer immunotherapy outcomes. – Targeting miRNAs that regulate exhaustion markers, such as PD-1 and TIM-3, holds promise for reinvigorating exhausted CD8+ T cells and unleashing their anti-tumor potential. – Developing effective delivery systems, such as nanoparticles or engineered T cells, for miRNA-based therapies within the TME is crucial for maximizing efficacy and minimizing off-target effects. *Correspondence: Sogand Vahidi[so.vahidii@gmail.com](so.vahidii@gmail.com) Full list of author information is available at the end of the article © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/.)[.](http://creativecommons.org/licenses/by-nc-nd/4.0/.) Zabeti Touchaei and Vahidi Journal of Translational Medicine (2024) 22:

FAQs

How do microRNAs regulate CD8+ T cell function in the tumor microenvironment (TME)?

The review explains that specific miRNAs influence CD8+ T cell activation, recruitment, infiltration, and effector function within the TME.

What role does miRNA dysregulation play in immune evasion?

Disordered miRNA regulation can contribute to CD8+ T cell exhaustion and immune evasion, which hinders effective anti-tumor immunity.

How might targeting miRNAs improve cancer immunotherapy?

Manipulating miRNA expression is presented as a promising strategy to enhance CD8+ T cell activity and improve immunotherapy outcomes, including approaches that target exhaustion markers.

Sep 21, 2026

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