Cold-inducible brown fat thermogenesis enhances MHC class I expression and antitumor immunity in ovarian cancer.

Brown adipose tissue (BAT) thermogenesis, induced by cold exposure or β3-adrenergic receptors (β3AR) agonist, decreases tumor glucose availability and arrests tumor progression. However, the effect of BAT activation on tumor metabolic reprogramming, the tumor microenvironment (TME), and the possibility of in combination with immunotherapy has not been defined. Here, we found that cold-inducible BAT thermogenesis promoted an anti-Warburg metabolic shift that reshaped TME characterized by accumulation of tumor-infiltrating CD8+ T cells (CD8+ TILs) with effector-like and memory phenotype and proinflammatory macrophages. Consistently, combination treatment with anti-PD-1 and cold exposure or β3AR agonist, strongly inhibited tumor growth or complete regressions across multiple preclinical mouse models. Therefore, BAT thermogenesis by cold exposure or β3aR agonist, highlighting a promising therapeutic approach to increase tumor immunogenicity and improve immunotherapy efficacy.