Genetic ablation of adipocyte PD-L1 reduces tumor growth but accentuates obesity-associated inflammation. Issue 2 (17th August 2020)

• Record Type: Journal Article
• Authors: Wu, Bogang; Chiang, Huai-Chin; Sun, Xiujie; Yuan, Bin; Mitra, Payal; Hu, Yanfen; Curiel, Tyler J; Li, Rong
• Is Part Of: Journal for immunotherapy of cancer. Volume 8:Issue 2(2020)
• Publication Date: 2020-08-17
• Subjects: immunity -- inflammation -- macrophages -- tumor microenvironment -- B7-H1 antigen; Cancer -- Immunotherapy -- Periodicals; Cancer -- Immunological aspects -- Periodicals; Tumors -- Immunological aspects -- Periodicals; Immunotherapy -- Periodicals; 616.99406105
• DOI: 10.1136/jitc-2020-000964
• Languages: English
• ISSNs: 2051-1426

Abstract

Abstract : The programmed death-ligand 1 (PD-L1)-dependent immune checkpoint attenuates host immunity and maintains self-tolerance. Imbalance between protective immunity and immunopathology due to altered PD-L1 signaling can lead to autoimmunity or tumor immunosuppression. The role of the PD-L1-dependent checkpoint in non-immune system is less reported. We previously found that white adipocytes highly express PD-L1. Here we show that adipocyte-specific PD-L1 knockout mice exhibit enhanced host anti-tumor immunity against mammary tumors and melanoma with low or no tumor PD-L1. However, adipocyte PD-L1 ablation in tumor-free mice also exacerbates diet-induced body weight gain, pro-inflammatory macrophage infiltration into adipose tissue, and insulin resistance. Low PD-L1 mRNA levels in human adipose tissue correlate with high body mass index and presence of type 2 diabetes. Therefore, our mouse genetic approach unequivocally demonstrates a cell-autonomous function of adipocyte PD-L1 in promoting tumor growth and inhibiting antitumor immunity. In addition, our work uncovers a previously unrecognized role of adipocyte PD-L1 in mitigating obesity-related inflammation and metabolic dysfunction.