articleSignal Transduction and Targeted TherapyJan 1, 2026GOLD OA

Revitalizing T cells: breakthroughs and challenges in overcoming T cell exhaustion

Second Affiliated Hospital of Zhejiang University · Shaoxing People's Hospital · +8 more institutions

PubMed
Indexed incrossrefdoajpubmed

Abstract

T cell exhaustion is a prevalent phenomenon in chronic infections and tumor microenvironments, severely compromising the effectiveness of antitumor and antiviral immunity. In recent years, there has been significant progress in understanding the underlying mechanisms of T cell exhaustion, including external factors and intrinsic cellular changes that drive this dysfunctional state. Key external factors such as persistent antigen exposure, immune checkpoint signaling, and the cytokine milieu, as well as intrinsic changes such as altered metabolic processes, epigenetic modifications, and transcriptional reprogramming, contribute to T cell dysfunction. Emerging therapies targeting T cell exhaustion aim to restore…

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