Bridging Mechanism and Monitoring: Checkpoint Biology, T-Cell Exhaustion, and Real-World Immune Biomarkers in Cancer Immunotherapy

Immune checkpoint inhibitors (ICIs) and newer anticancer agents, including antibody-drug conjugates (ADCs) and next-generation checkpoint therapies (e.g., targeting LAG-3, TIGIT, TIM-3), have expanded treatment options across solid tumors, but a large share of patients still fail to respond or develop resistance. Two research communities currently work on this problem largely in parallel: mechanistic immunology, which defines how T-cell exhaustion and tumor-driven immunosuppression develop at the molecular level, and clinical/translational oncology, which tracks patient-level immune changes and real-world outcomes during treatment. Few collections connect the two directly.This Research Topic focuses on that connection: how mechanisms of T-cell exhaustion, checkpoint receptor biology, and tumor microenvironment immunosuppression translate into measurable, trackable changes in patients undergoing treatment with ICIs, ADCs, and emerging checkpoint-targeted therapies. We welcome studies spanning molecular mechanisms, peripheral and tissue biomarker correlates, and real-world clinical outcomes. Work that links a defined mechanism (e.g., a specific checkpoint receptor or a metabolic or epigenetic driver of suppression) to a clinical monitoring approach or outcome is particularly encouraged, though not required. Strong contributions in a single lane are equally welcome.We welcome Original Research, Reviews, and Case Reports covering, but not limited to:- Molecular and metabolic-epigenetic drivers of T-cell exhaustion or tumor-driven immunosuppression, ideally with a discussion of clinical relevance or monitoring implications- Biology of next-generation checkpoint targets (LAG-3, TIGIT, TIM-3, VISTA, and others) as they relate to treatment response or resistance in patients- Peripheral immune-cell profiling, cytokine/proteomic signatures, and liquid biopsy (CTC, ctDNA) as tools for tracking exhaustion- or suppression-related mechanisms during treatment- Real-world clinical data on immune dynamics and outcomes with ICIs, ADCs, and next-generation checkpoint agents (e.g., tarlatamab, trastuzumab deruxtecan, LAG-3/TIGIT-targeted therapies)- Studies correlating mechanistic or tissue-level findings with peripheral or blood-based monitoring dataPlease also note that manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases, which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo), are out of scope for this Research Topic. Topic editors: Juwhan Choi, Vaishali Aggarwal, Jieliang Zuo Source: https://www.frontiersin.org/research-topics/85377/bridging-mechanism-and-monitoring-checkpoint-biology-t-cell-exhaustion-and-real-world-immune-biomarkers-in-cancer-immunotherapy