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Transient activation of tumor-associated macrophages boosts anti-tumor immunity

ABSTRACT: Depletion of immunosuppressive tumor-associated macrophages (TAM) or reprogramming towards a pro-inflammatory activation state represent different strategies to therapeutically target this frequent myeloid population. Here we report that inhibition of colony-stimulating factor-1 receptor (CSF-1R) signaling sensitizes TAM to profound reprogramming in the presence of a CD40 agonist prior to their depletion. Despite the short-lived nature of macrophage hyperactivation, combined CSF-1R/CD40 stimulation of macrophages is sufficient to trigger a productive and durable T cell response in various mouse cancer models. The central role of macrophages in regulating T cell-dependent tumor rejections was substantiated by depletion experiments and transcriptomic analysis of ex vivo sorted TAM. Since CD40 expression on human TAM varies between different tumor types, co-expression of human CSF-1R and CD40 in colorectal adenocarcinoma and mesothelioma can serve as criteria to select these tumor types for clinical development

ORGANISM(S): Mus musculus

PROVIDER: GSE99808 | GEO | 2018/01/08

SECONDARY ACCESSION(S): PRJNA389686

REPOSITORIES: GEO

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