Checkpoint Pathways and Immunosuppressive Cell States in Cancer: Multi-Omics Mechanisms and Biomarkers.

Immune-oncology is rapidly evolving through the integration of single-cell and multi-omics approaches, which have transformed our understanding of how immune checkpoint pathways and immunosuppressive cell states contribute to tumor progression and therapeutic resistance. Traditional bulk genomic and transcriptomic analyses have illuminated key regulatory mechanisms, but are limited in their ability to resolve the heterogeneity and spatial dynamics of the tumor microenvironment. Recent advances in single-cell RNA sequencing, spatial transcriptomics, and multimodal profiling now enable unprecedented mapping of cellular interactions and regulatory states underpinning immune escape. These technologies have revealed previously unappreciated suppressive populations, complex cell-state transitions, and spatially organized immune niches that govern checkpoint activity—yet many questions remain about how these features evolve across cancer types and under selective pressure from immunotherapy. Despite significant progress, there are ongoing debates about the universality of certain biomarkers, the context-specificity of immune regulation, and the mechanisms of resistance to checkpoint inhibitors.This Research Topic aims to advance mechanistic and translational understanding of checkpoint pathways and immunosuppressive cell states in cancer through cutting-edge multi-omics approaches, with a particular emphasis on single-cell resolution and integrative analyses. Key objectives include dissecting the regulatory architecture and plasticity of suppressive cellular programs, mapping checkpoint signaling within the tumor microenvironment, and translating these insights into novel biomarkers for prognosis and immunotherapy response prediction. We seek to address outstanding questions regarding cell-state discovery, lineage trajectories, and the interplay between genetic, epigenetic, and spatial determinants of immune regulation. By linking mechanistic insights with clinical outcomes, the Research Topic aspires to foster precision medicine strategies that can overcome resistance and optimize immunotherapeutic interventions.This Research Topic welcomes original research, reviews, methods, and perspectives that leverage single-cell and multi-omics technologies to study checkpoint pathways and immunosuppressive cell states in cancer. Contributions employing integrative data analysis, robust marker validation, and translational links to patient outcomes are especially encouraged. Topics of interest include, but are not limited to:• Single-cell and spatial multi-omics of checkpoint regulation and immune dysfunction (e.g., exhaustion, anergy)• Cell-state discovery, lineage trajectories, and plasticity of suppressive populations (Tregs, MDSCs, TAMs, exhausted T cells)• Multi-omics integration frameworks (scRNA-seq/scATAC-seq, CITE-seq, spatial transcriptomics) and cell–cell communication analyses• Cross-cohort validation of biomarkers and signatures for prognosis and prediction of immunotherapy response or toxicity• Mechanisms of primary and adaptive resistance and combination immunotherapy strategies informed by multi-omics• Translational studies linking omics-derived immune cell states to clinical outcomes and treatment response Topic editors: Jian Wang, Xin Li Source: https://www.frontiersin.org/research-topics/78002/checkpoint-pathways-and-immunosuppressive-cell-states-in-cancer-multi-omics-mechanisms-and-biomarkers