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Single-cell transcriptomics reveals the natural product cannabinoid rewires tumor microenvironment via inhibiting alternative activation of macrophage and synergizes with PD-1 blockade

ABSTRACT: Colorectal tumors often display a suppressive immune microenvironment that limits their response to immunotherapy. Here, we report that Cannabidiol, a natural non-psychoactive constituent of the cannabis plant, inhibits colorectal cancer progression by modulating the suppressive tumor microenvironment. Our single-cell transcriptome sequencing results showed that CBD inhibits M2-polarized macrophages while promoting M1-polarized macrophages, which restores the intrinsic antitumor properties of macrophages to inhibit tumor progression. Mechanistically, CBD inhibits alternative activation of macrophages by inhibiting PI3K-Akt signaling, which shifts cell metabolism from oxidative phosphorylation and fatty acid oxidation to glycolysis. Moreover, CBD-mediated macrophage plasticity enhanced the response to anti-PD1 immunotherapy in xenograft mice. Taken together, our study provides new insights into the antitumor effects of CBD.

ORGANISM(S): Mus musculus

PROVIDER: GSE220635 | GEO | 2023/09/29

REPOSITORIES: GEO

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