An IL-4 signalling axis in bone marrow drives pro-tumorigenic myelopoiesis.

ABSTRACT: Myeloid cells are known to suppress antitumour immunity¹. However, the molecular drivers of immunosuppressive myeloid cell states are not well defined. Here we used single-cell RNA sequencing of human and mouse non-small cell lung cancer (NSCLC) lesions, and found that in both species the type 2 cytokine interleukin-4 (IL-4) was predicted to be the primary driver of the tumour-infiltrating monocyte-derived macrophage phenotype. Using a panel of conditional knockout mice, we found that only deletion of the IL-4 receptor IL-4Rα in early myeloid progenitors in bone marrow reduced tumour burden, whereas deletion of IL-4Rα in downstream mature myeloid cells had no effect. Mechanistically, IL-4 derived from bone marrow basophils and eosinophils acted on granulocyte-monocyte progenitor

SUBMITTER: LaMarche NM 

PROVIDER: S-EPMC11189607 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature