Frontiers in Immunology
Radiomics and deep learning for immune checkpoint inhibitor outcomes: imaging-derived immune phenotyping and clinical translation across solid tumors
By Hangyu Wu and Jing Chen.
Abstract
Immune checkpoint inhibitors (ICIs) have transformed the treatment of multiple solid tumors, but durable benefit remains restricted to a subset of patients and conventional size-based imaging does not fully capture immune-related response patterns. Radiomics and deep learning offer a route to convert routine CT, MRI, and PET/CT into quantitative biomarkers of tumor phenotype, whole-body heterogeneity, and temporal treatment response. This narrative review critically synthesizes the evidence across solid tumors with an emphasis on four questions that are often separated in the literature: what added information is provided by different AI approaches, whether imaging signatures can be interpreted as non-invasive immune phenotypes, how methodological choices determine reproducibility, and what evidence is required for clinical translation. CT currently has the broadest outcome-prediction literature, particularly in non-small cell lung cancer; MRI provides complementary diffusion, perfusion, and soft-tissue information in hepatocellular carcinoma and brain metastases; and PET/CT adds metabolic and whole-body measures that may reflect both tumor burden and immune-metabolic state. Associations with CD8-positive T-cell infiltration, PD-L1 expression, tumor immune microenvironment states, response, progression-free survival, and overall survival support biological plausibility, but they do not establish treatment-specific predictive utility. We compare handcrafted radiomics, classical machine learning, convolutional neural networks, transformer-based approaches, self-supervised learning, and emerging foundation models, and discuss explainable AI, longitudinal imaging, pseudoprogression, and hyperprogressive disease. Major barriers remain small retrospective cohorts, high-dimensional feature selection, data leakage, scanner and protocol effects, treatment heterogeneity, selective reporting, weak calibration, and limited external or prospective validation. At present, AI-derived imaging biomarkers are best considered investigational decision-support tools. Their most credible near-term role is to complement, rather than replace, established clinical and molecular biomarkers; multimodal strategies that combine imaging with tissue, circulating, and clinical data remain promising but require demonstration of incremental and prospective clinical utility.





