MerTK⁺ macrophages promote melanoma progression and immunotherapy resistance through AhR-ALKAL1 activation.

ABSTRACT: Despite our increasing understanding of macrophage heterogeneity, drivers of macrophage phenotypic and functional polarization in the microenvironment are not fully elucidated. Here, our single-cell RNA sequencing data identify a subpopulation of macrophages expressing high levels of the phagocytic receptor MER proto-oncogene tyrosine kinase (MerTK⁺ macrophages), which is closely associated with melanoma progression and immunotherapy resistance. Adoptive transfer of the MerTK⁺ macrophages into recipient mice notably accelerated tumor growth regardless of macrophage depletion. Mechanistic studies further revealed that ALK And LTK Ligand 1 (ALKAL1), a target gene of aryl hydrocarbon receptor (AhR), facilitated MerTK phosphorylation, resulting in heightened phagocytic ac

SUBMITTER: Wu N 

PROVIDER: S-EPMC11451552 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature