Immunogenomic Biomarkers for Precision Immunotherapy: From HLA and Neoantigens to Co‑stimulatory Pathways

Cancer immunotherapy has transformed outcomes for many patients, yet durable benefit remains limited to subsets of individuals and tumor types. This variability reflects the complex interplay between tumor genomics, antigen presentation, immune recognition, and the regulatory circuits that shape effective (or ineffective) anti-tumor immunity. As precision oncology moves beyond tumor-intrinsic alterations alone, immunogenomic biomarkers—spanning germline and somatic variation, tumor antigenicity, and immune modulatory pathways—are increasingly central for predicting response, resistance, toxicity, and for guiding rational therapeutic combinations.This Research Topic focuses on immunogenomic biomarkers for precision immunotherapy, emphasizing the continuum from HLA biology and antigen presentation to neoantigen landscapes and co‑stimulatory/co‑inhibitory signaling. We welcome contributions that advance mechanistic understanding, improve biomarker discovery and validation, and accelerate translation into clinically deployable strategies for patient stratification and treatment optimization across solid tumors and hematologic malignancies.Manuscripts addressing, but not limited to, the following are especially of interest for this collection:• HLA and antigen processing/presentation: germline HLA diversity, HLA loss of heterozygosity, tumor escape via antigen presentation defects, immunopeptidomics, and clinical implications for checkpoint blockade and cellular therapies.• Neoantigens and tumor antigenicity: neoantigen prediction and prioritization, clonal vs. subclonal neoantigens, post-translationally modified antigens, viral and endogenous retroelement-derived antigens, and links to T-cell repertoire dynamics.• Immunogenomic determinants of response and resistance: tumor mutational burden and beyond, DNA repair defects, oncogenic pathways shaping immune exclusion, interferon signaling, antigen evolution under therapeutic pressure, and biomarkers of hyperprogression or immune escape.• Co‑stimulatory and immune regulatory pathways: genomic and transcriptomic markers related to co‑stimulatory targets (e.g., TNFR superfamily members) and immune suppressive circuits in the tumor microenvironment, including how these inform combination strategies with checkpoint blockade, vaccines, bispecifics, or adoptive cell therapy.• Clinical translation and implementation: biomarker-driven trial design, assay harmonization, multi-omic integration, and real-world feasibility (tissue and liquid biopsy), with attention to robustness, reproducibility, and clinically meaningful endpoints.• Submissions centered primarily on computational analyses of public datasets or Mendelian randomisation should include appropriate validation (e.g., independent cohorts and/or biological validation) to support actionable conclusions.This collection aims to clarify which immunogenomic features are most informative, how they should be measured, and how they can be leveraged to improve the precision, safety, and durability of cancer immunotherapy.Please note: Manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent clinical or patient cohort, or biological validation in vitro or in vivo, which are not based on public databases) are not suitable for publication in this journal. Topic editors: Razelle Kurzrock, Myrto K. Moutafi Source: https://www.frontiersin.org/research-topics/79066/immunogenomic-biomarkers-for-precision-immunotherapy-from-hla-and-neoantigens-to-co-stimulatory-pathways