Omics-driven insights into tumor microenvironment determinants of immunotherapy response in cancer

Immunotherapy has revolutionized cancer treatment, yet response rates remain highly variable across tumor types and individual patients. Increasing evidence indicates that the tumor microenvironment (TME) plays a central role in shaping therapeutic outcomes. The TME is a complex and dynamic ecosystem composed of immune cells, stromal components, vasculature, extracellular matrix, and soluble factors that collectively influence tumor progression and immune evasion. Recent advances in omics technologies—including genomics, transcriptomics, proteomics, metabolomics, and single-cell and spatial multi-omics—have enabled unprecedented characterization of TME heterogeneity. These high-dimensional approaches are uncovering molecular determinants of immune activation, suppression, and resistance mechanisms. A systems-level understanding of these determinants is essential to identify predictive biomarkers and develop more effective, personalized immunotherapeutic strategies.This Research Topic aims to elucidate the omics-driven molecular and cellular determinants within the tumor microenvironment that influence response or resistance to immunotherapy. Despite major breakthroughs with immune checkpoint inhibitors, CAR-based therapies, and cancer vaccines, durable responses are limited to subsets of patients. The underlying mechanisms often involve complex interactions between tumor-intrinsic features and microenvironmental components such as immune cell composition, metabolic reprogramming, stromal remodelling, and spatial organization. By integrating multi-omics datasets with advanced computational and systems biology approaches, recent studies have begun to identify predictive signatures and actionable pathways associated with therapeutic efficacy. However, translation into clinically robust biomarkers remains challenging. This Topic seeks to bridge this gap by promoting research that combines high-resolution omics profiling, functional validation, and translational modelling. Contributions addressing novel biomarkers, resistance mechanisms, and innovative strategies to modulate the TME to enhance immunotherapy response are particularly encouraged.This Research Topic welcomes original research articles, reviews, mini-reviews, and methodological papers focusing on omics-based investigations of tumor microenvironment determinants of immunotherapy response.Specific themes of interest include:• Genomic and transcriptomic predictors of immunotherapy response• Single-cell and spatial multi-omics analyses of the TME• Proteomic and metabolomic profiling of immune modulation• Computational integration of multi-omics datasets• Mechanisms of immune resistance mediated by stromal or metabolic factors• Biomarker discovery and validation for patient stratification• Systems biology and AI-driven modelling of TME–immune interactions• Translational studies linking omics signatures to clinical outcomesSubmissions combining experimental and computational approaches, as well as studies with clear translational relevance are particularly encouraged.Please 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: Italia Falcone, Cristina Sorino, Mouayad Masalkhi, Grant Fischer Source: https://www.frontiersin.org/research-topics/78934/omics-driven-insights-into-tumor-microenvironment-determinants-of-immunotherapy-response-in-cancer