Phenotypic plasticity and increased infiltration of peripheral blood-derived TREM1⁺ mono-macrophages following radiotherapy in rectal cancer.

ABSTRACT: In our previously reported phase 2 and phase 3 studies, the combination of short-course radiotherapy and neoadjuvant immunochemotherapy (SIC) is established as effective cancer therapies for locally advanced rectal cancer (LARC). Here, we apply multi-omic analyses to paired pre- and post-treatment LARC specimens undergoing SIC. The peripheral blood-derived TREM1⁺ mono-macrophage subsets that display a pro-inflammatory phenotype are identified and correlate with complete response to SIC. Mechanically, ionizing radiation (IR) induces peripheral TREM1⁺ mono-macrophage expansion in tumors. Following IR, the loss of TREM1 in mono-macrophages undermines antitumor immunity by altering mono-macrophage differentiation and inhibiting CD8⁺ T cell infiltration and acti

SUBMITTER: Wang H 

PROVIDER: S-EPMC11866444 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature