Liver metastasis restrains immunotherapy efficacy via macrophage-mediated T cell elimination.

ABSTRACT: Metastasis is the primary cause of cancer mortality, and cancer frequently metastasizes to the liver. It is not clear whether liver immune tolerance mechanisms contribute to cancer outcomes. We report that liver metastases diminish immunotherapy efficacy systemically in patients and preclinical models. Patients with liver metastases derive limited benefit from immunotherapy independent of other established biomarkers of response. In multiple mouse models, we show that liver metastases siphon activated CD8⁺ T cells from systemic circulation. Within the liver, activated antigen-specific Fas⁺CD8⁺ T cells undergo apoptosis following their interaction with FasL⁺CD11b⁺F4/80⁺ monocyte-derived macrophages. Consequently, liver metast

SUBMITTER: Yu J 

PROVIDER: S-EPMC8095049 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature