Session 4 : Molecular mechanisms of resistance

Clonal Hematopoiesis in Cancer

Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition associated with increased mortality in patients with cancer. CHIP mutations with high variant allele frequencies can be detected in tumors, a phenomenon we term tumor-infiltrating clonal hematopoiesis (TI-CH). We characterized TI-CH in 421 patients with early-stage non-small cell lung cancer (NSCLC) from the TRACERx study and 49,351 patients from the MSK-IMPACT pan-cancer cohort. We studied the association of TI-CH with survival and disease recurrence and evaluated the functional impact of TET2-mutant-CHIP on lung tumor biology. TI-CH increased the risk of death or recurrence in NSCLC and of all-cause mortality in solid tumors. TI-CH remodeled the tumor immune microenvironment and accelerated tumor organoid growth, supporting a role for an aging-related hematologic clonal proliferation in cancer evolution.