196-TET2-Mutant Hematopoiesis Enhances ICT Response

This article details research on how TET2-mutant clonal hematopoiesis (CH) affects the response to immune checkpoint therapy (ICT) in solid tumors. The authors demonstrate that the presence of the TET2 mutation in myeloid cells, specifically macrophages, enhances their ability to function as antigen-presenting cells, particularly in response to IFNγ signaling. Through mouse models and analysis of large human cohorts with non-small cell lung and colorectal cancers, the study establishes that TET2-mutant CH improves overall patient survival only in those receiving ICT, suggesting it could serve as a valuable biomarker for predicting immunotherapy response. The core mechanism involves these TET2-mutant macrophages effectively priming cytotoxic CD8+ T cells to attack the tumor.

References:

• Herbrich, Shelley, et al. "TET2-mutant clonal hematopoiesis enhances macrophage antigen presentation and improves immune checkpoint therapy in solid tumors." Cancer Cell (2025).