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

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

Research output: Contribution to journalArticle

6 Scopus citations

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.

Original languageEnglish (US)
Article numbere1500107
JournalOncoImmunology
Volume7
Issue number11
DOIs
StatePublished - Nov 2 2018

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Keywords

  • Breast cancer
  • PD-1
  • PD-L1
  • PPARgamma antagonist
  • adipocyte
  • combination therapy
  • immune checkpoint
  • immunotherapy
  • inflammation and cancer
  • new targets

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

Cite this

Wu, B., Sun, X., Gupta, H. B., Yuan, B., Li, J., Ge, F., Chiang, H. C., Zhang, X., Zhang, C., Zhang, D., Yang, J., Hu, Y., Curiel, T. J., & Li, R. (2018). Adipose PD-L1 Modulates PD-1/PD-L1 Checkpoint Blockade Immunotherapy Efficacy in Breast Cancer. OncoImmunology, 7(11), [e1500107]. https://doi.org/10.1080/2162402X.2018.1500107