Adipose PD-L1 Modulates PD-1/PD-L1 Checkpoint Blockade Immunotherapy Efficacy in Breast Cancer.

Abstract

Programmed death-ligand 1 (PD-L1) and its receptor programmed cell death protein 1 (PD-1) modulate antitumor immunity and are major targets of checkpoint blockade immunotherapy. However, clinical trials of anti-PD-L1 and anti-PD-1 antibodies in breast cancer demonstrate only modest efficacy. Furthermore, specific PD-L1 contributions in various tissue and cell compartments to antitumor immunity remain incompletely elucidated. Here we show that PD-L1 expression is markedly elevated in mature adipocytes versus preadipocytes. Adipocyte PD-L1 prevents anti-PD-L1 antibody from activating important antitumor functions of CD8+ T cells in vitro. Adipocyte PD-L1 ablation obliterates, whereas forced preadipocyte PD-L1 expression confers, these inhibitory effects. Pharmacologic inhibition of adipogenesis selectively reduces PD-L1 expression in mouse adipose tissue and enhances the antitumor efficacy of anti-PD-L1 or anti-PD-1 antibodies in syngeneic mammary tumor models. Our findings provide a previously unappreciated approach to bolster anticancer immunotherapy efficacy and suggest a mechanism for the role of adipose tissue in breast cancer progression.

• Authors: Bogang Wu, Xiujie Sun, Harshita B Gupta, Bin Yuan, Jingwei Li, Fei Ge, Huai-Chin Chiang, Xiaowen Zhang, Chi Zhang, Deyi Zhang, Jing Yang, Yanfen Hu, Tyler J Curiel, Rong Li
• Journal: Oncoimmunology (Oncoimmunology) 2018 Vol. 7 Issue 11 Pg. e1500107 ISSN: 2162-4011 [Print] United States
• PMID: 30393583 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural)