Frontiers in Immunology · Nov 3, 2026
Mutation-Specific Immune Programs in Clonal Hematopoiesis: Implications for Solid Tumor Biology and Immunotherapeutic Approaches
By Qierra R Brockman, Cailin Collins, James DeGregori et al.
Clonal hematopoiesis (CH) is an age-associated condition driven by the expansion of hematopoietic stem cells (HSCs) harboring somatic driver mutations, most commonly DNMT3A and TET2. Traditionally, CH is associated with myeloid skewing, chronic inflammation, and increased leukemic risk. CH is now recognized as a systemic modifier of immune states and function with broad implications for inflammatory diseases and cancer. In solid tumors, emerging evidence suggests that CH may exert context-dependent effects on anti-tumor immunity, with studies reporting tumor-promoting phenotypes associated with myeloid-driven inflammation as well as enhanced antigen presentation machinery and anti-tumor immune responses in specific experimental and treatment contexts. These seemingly opposing effects may reflect mutation-specific programs that differentially rewire myeloid and lymphoid compartments, influencing cytokine signaling, and T cell function. In this review, we synthesize current understanding of CH biology with a focus on mutation-associated immune phenotypes and their potential implications for the solid tumor microenvironment. We highlight evidence that CH-associated inflammation encompasses a spectrum of immune states that can be tumor-promoting or therapeutically advantageous depending on genotype, hematopoietic lineage, tumor context, and treatment exposure. Collectively, these emerging findings support further investigation of CH as a context-dependent modifier of cancer immunity and as a potential biomarker or therapeutic consideration for future immunomodulatory strategies.