Clonal hematopoiesis of indeterminate potential and cancer immunotherapy: a host-intrinsic immune-inflammatory modifier of treatment efficacy and toxicity.

Clonal hematopoiesis of indeterminate potential (CHIP), the age-related expansion of hematopoietic stem cells carrying leukemia-associated somatic mutations, is common in patients with cancer and is increasingly detected during tumor-only genomic profiling and cell-free DNA sequencing. In this narrative review, we assess epidemiological, mechanistic, and clinical evidence at the interface between CHIP and cancer immunotherapy using a three-level hierarchy: established inflammatory biology, suspected effects on antitumor immunity, and unresolved direct human causality. We also map the evidence by driver gene, clone size, tumor type, treatment modality, and detection context. Immunotherapy-specific data are concentrated in TET2-mutant CHIP; associations for DNMT3A and ASXL1 are weaker, and direct JAK2 data are absent. Clinical ICI cohorts report favorable TET2-associated efficacy signals and no evidence that checkpoint blockade selects CH clones. Separate studies associate CHIP with ICI myocarditis and with severe cytokine release syndrome, prolonged hematologic toxicity, and TP53-mutant clonal expansion after CAR T-cell therapy. These findings remain observational and context dependent. Current evidence does not support CHIP-guided treatment selection. Prospective, standardized studies are needed to determine whether specific CHIP phenotypes predict efficacy, toxicity, or neither.