Omics-based biomarkers of immune-related organ toxicities associated with immune checkpoint inhibitors: a scoping review and evidence map.

BACKGROUND: Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs) across multiple organs. High-throughput omics approaches may help characterize susceptibility, molecular mechanisms, diagnostic features, and monitoring markers related to irAEs; however, evidence remains dispersed across platforms, clinical applications, and toxicity phenotypes.

OBJECTIVE: To map original human evidence in which high-throughput omics approaches were directly linked to irAE susceptibility, occurrence, severity, diagnosis, longitudinal monitoring, clinical course, recovery, response to irAE-directed treatment, or mechanistic characterization. Methods: This scoping review and evidence map followed a registered protocol and was informed by PRISMA-ScR and JBI guidance. PubMed/MEDLINE, Scopus, Web of Science Core Collection, and Embase were searched from January 1, 2014, with the final database search completed on July 9, 2026. Eligible studies involved ICI-exposed patients or human biospecimens, implemented high-throughput genomics/statistical genetics, transcriptomics, proteomics, metabolomics/lipidomics, microbiome/metagenomics, single-cell or spatial omics, immune-repertoire sequencing, or integrated multi-omics approaches, and directly evaluated an irAE outcome. Genome-wide statistical-genetic studies were retained as a conditional evidence category. Targeted single-marker studies, routine laboratory biomarkers, efficacy-only omics analyses, non-ICI populations, non-original reports, case reports, and preclinical-only omics studies were excluded.

RESULTS: The searches identified 4,669 records. After removal of 1,151 duplicates, 3,518 unique records were screened and 433 reports were sought for retrieval. Thirty-two reports could not be retrieved for full-text assessment. Of 401 reports assessed in full text, 315 were excluded and 86 studies were included. Omics domains were non-mutually exclusive: transcriptomics was used in 50 studies, single-cell/spatial omics in 31, proteomics in 20, microbiome/metagenomics in 20, immune-repertoire sequencing in 16, genomics/statistical genetics in 14, and metabolomics/lipidomics in 6. Forty-seven studies contributed to two or more omics domains in the platform audit; after accounting for overlapping analytical modalities, 35 studies met the predefined criteria for true multi-omics integration involving independent molecular layers. Forty-five studies addressed mixed or general irAEs; among organ-specific studies, myocarditis/cardiovascular toxicity (n=10), pneumonitis/lung toxicity (n=9), and gastrointestinal/colitis toxicity (n=8) were most frequent.

CONCLUSIONS: The high-throughput omics literature directly evaluating irAEs is substantially smaller than the broader biomarker literature and is dominated by transcriptomic and single-cell approaches. Most evidence remains exploratory, with limited independent assessment of predefined models or signatures, incomplete coverage of endocrine, renal, neurologic, hematologic, pancreatic, and musculoskeletal toxicities, and substantial gaps between molecular discovery and clinical implementation. Prospective multicenter cohorts, standardized irAE phenotyping, longitudinal sampling, and independent validation are required to support clinical implementation. Future studies integrating multiple molecular layers with advanced computational approaches may improve biomarker discovery and individualized risk stratification but require transparent development and rigorous validation.

SYSTEMATIC REVIEW REGISTRATION: https://osf.io/g79cv, identifier g79cv.