Chloroquine modulates antitumor immune response by resetting tumor-associated macrophages toward M1 phenotype.

ABSTRACT: Resetting tumor-associated macrophages (TAMs) is a promising strategy to ameliorate the immunosuppressive tumor microenvironment and improve innate and adaptive antitumor immunity. Here we show that chloroquine (CQ), a proven anti-malarial drug, can function as an antitumor immune modulator that switches TAMs from M2 to tumor-killing M1 phenotype. Mechanistically, CQ increases macrophage lysosomal pH, causing Ca²⁺ release via the lysosomal Ca²⁺ channel mucolipin-1 (Mcoln1), which induces the activation of p38 and NF-κB, thus polarizing TAMs to M1 phenotype. In parallel, the released Ca²⁺ activates transcription factor EB (TFEB), which reprograms the metabolism of TAMs from oxidative phosphorylation to glycolysis. As a result, CQ-reset macrophages ameliorate

SUBMITTER: Chen D 

PROVIDER: S-EPMC5830447 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature