T Cell Exhaustion in Chronic Infection and Cancer

T cell exhaustion, a state of T cell dysfunction driven by persistent antigen exposure, is a hallmark of chronic viral infections and cancer. Characterized by progressive loss of effector function, sustained expression of inhibitory receptors (e.g., PD-1, CTLA-4, TIM-3, LAG-3), and distinct transcriptional and epigenetic changes, exhaustion enables pathogen persistence and tumor immune evasion. While immune checkpoint blockade (ICB) has shown remarkable success in reinvigorating exhausted T cells, therapeutic responses remain variable, underscoring the need to better understand the mechanisms underlying exhaustion and its heterogeneity.This collection aims to explore the molecular drivers, microenvironmental influences, and therapeutic strategies targeting T cell exhaustion. Key areas of focus include:• Transcriptional and epigenetic regulation: Insights into the gene networks and chromatin remodeling that sustain exhaustion.• Metabolic reprogramming: How metabolic shifts in nutrients, mitochondria, and signaling pathways contribute to T cell dysfunction.• Heterogeneity and subsets: The diversity of exhausted T cell populations and their functional implications in disease contexts.• Microenvironmental cues: The role of cytokines, stromal cells, and immune suppressive factors in promoting exhaustion.• Novel biomarkers and predictors: Identifying signatures to predict response to immunotherapy.• Emerging therapies: Advances in combination therapies, adoptive cell transfer (e.g., CAR-T, TCR-T), gene editing, and small molecule inhibitors.By integrating cutting-edge research and reviews, this collection aims to provide a comprehensive resource for understanding T cell exhaustion and its therapeutic potential. We invite original research, reviews, and perspectives that advance the field, offering new insights into overcoming T cell dysfunction to improve outcomes in chronic infections and cancer. Topic editors: Ying Luo, Qun Lin, Xiaosheng Tan Source: https://www.frontiersin.org/research-topics/70168/t-cell-exhaustion-in-chronic-infection-and-cancer