Biomarkers, Mechanisms, and Therapeutic Strategies of Immune Checkpoint Blockade for Cancers

Immune checkpoint blockade (ICB) has reshaped modern immunotherapy by unleashing antitumor immune responses through targeting inhibitory immune checkpoints such as PD-1, PD-L1, and CTLA-4. Despite its transformative impact, the mechanisms governing therapeutic response, resistance, and immune-related toxicity remain incompletely understood. Increasing evidence indicates that ICB efficacy is determined by highly dynamic and heterogeneous immune states shaped by cellular interactions, clonal evolution, and microenvironmental cues. Recent advances in high-dimensional and data-driven technologies—including single-cell and spatial transcriptomics, multi-omics profiling, high-throughput immune repertoire sequencing, and computational modeling—have enabled unprecedented resolution in dissecting immune mechanisms underlying ICB. These approaches reveal complex regulatory programs across diverse immune populations, uncover novel functional cell states, and provide quantitative frameworks to link molecular mechanisms with therapeutic outcomes.This Research Topic aims to highlight mechanistic and data-driven studies that elucidate the cellular and molecular principles of immune checkpoint blockade. We particularly encourage integrative analyses that leverage large-scale datasets, advanced computational methods, and functional validation to uncover causal mechanisms of ICB response and resistance. While clinical relevance is important, the primary emphasis of this collection is on mechanistic insight and systems-level understanding, with translational implications as a secondary focus.Topics of Interest include, but are not limited to:• Mechanistic dissection of immune checkpoint signaling and downstream regulatory networks• Data-driven identification of immune cell states and trajectories during ICB therapy• Single-cell, spatial, and multi-omics analyses of tumor–immune interactions• Computational modeling and systems immunology approaches to ICB mechanisms• Integration of immune repertoire sequencing with transcriptomic and epigenomic data• Mechanisms of intrinsic and acquired resistance to immune checkpoint blockade• Functional validation of novel immune checkpoints or regulatory pathways revealed by omics analyses• Translational implications of mechanistic discoveries for biomarker development and therapeutic strategiesThis Research Topic focuses on elucidating the mechanisms, biomarkers, and therapeutic strategies of immune checkpoint blockade (ICB) from a mechanistic and systems immunology perspective. We aim to bring together studies that dissect the cellular and molecular principles governing ICB response, resistance, and immune-related toxicity. Emphasis is placed on the dynamic and heterogeneous immune states shaped by cellular interactions, clonal evolution, and tumor microenvironmental cues. We particularly welcome data-driven and integrative studies leveraging single-cell and spatial transcriptomics, multi-omics profiling, immune repertoire sequencing, and advanced computational modeling to uncover causal mechanisms underlying ICB efficacy. Contributions addressing T cell functional states, non–T cell immune populations, immune checkpoint signaling networks, and mechanisms of intrinsic or acquired resistance are encouraged. While translational relevance and biomarker discovery are of interest, the primary focus is on mechanistic insight and systems-level understanding. Manuscript types include Original Research Articles, Brief Research Reports, Reviews, and Perspectives that advance our understanding of ICB biology and inform future therapeutic strategies. Topic editors: Fuduan Peng, Yanshuo Chu, ZHOU Xunian Source: https://www.frontiersin.org/research-topics/80232/biomarkers-mechanisms-and-therapeutic-strategies-of-immune-checkpoint-blockade-for-cancers