Genetic ablation of adipocyte PD-L1 reduces tumor growth but accentuates obesity-associated inflammation
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 01, 2020
- Source ID
- 10.1136/jitc-2020-000964
Entities
People
- Bin Yuan
- Bogang Wu
- Huai-chin Chiang
- Payal Mitra
- Rong Li
- Tyler J Curiel
- Xiujie Sun
- Yanfen Hu
Organizations
- National Institutes of Health
- United States Department of Defense