2. Academic Validation
  3. Gasdermin D restricts anti-tumor immunity during PD-L1 checkpoint blockade

Gasdermin D restricts anti-tumor immunity during PD-L1 checkpoint blockade

  • Cell Rep. 2022 Oct 25;41(4):111553. doi: 10.1016/j.celrep.2022.111553.
Yuying Jiang 1,  Yongbing Yang 1,  Yingchao Hu 1,  Rui Yang 1,  Jiajia Huang 2,  Yi Liu 1,  Yuqing Wu 3,  Sheng Li 1,  Chunmei Ma 1,  Fiachra Humphries 4,  Bingwei Wang 5,  Xi Wang 6,  Zhibin Hu 7,  Shuo Yang 8
Affiliations

Affiliations

  • 1 Department of Immunology, State Key Laboratory of Reproductive Medicine, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Gusu School, Nanjing Medical University, Nanjing 211166, China.
  • 2 Department of Pharmacology, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing 210023, China.
  • 3 Department of Immunology, State Key Laboratory of Reproductive Medicine, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Gusu School, Nanjing Medical University, Nanjing 211166, China; Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, National Key Clinical Department of Laboratory Medicine, Nanjing 210029, China.
  • 4 Department of Medicine, UMass Chan Medical School, Worcester, MA 01605, USA.
  • 5 Department of Pharmacology, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing 210023, China. Electronic address: [email protected].
  • 6 State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, China. Electronic address: [email protected].
  • 7 State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, China; Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China. Electronic address: [email protected].
  • 8 Department of Immunology, State Key Laboratory of Reproductive Medicine, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Gusu School, Nanjing Medical University, Nanjing 211166, China. Electronic address: [email protected].
PMID: 36288704 DOI: 10.1016/j.celrep.2022.111553
Abstract

Tumor microenvironments (TMEs) require co-operation of innate and adaptive immune cells, which influence tumor progression and immunotherapy. Caspase-activated gasdermins facilitate tumor death and promote anti-tumor immunity. How Pyroptosis in immune cells affects the TME remains unclear. TME expression of gasdermin D (GSDMD) is highly expressed in antigen-presenting cells (APCs) and correlates with immune checkpoint signatures. Through conditional deletion of GSDMD, we demonstrate that GSDMD in TME APCs restricts anti-tumor immunity during PD-L1 inhibition. Loss of GSDMD in APCs enhances interferon-stimulated genes (ISGs), thereby promoting CD8+ T cell activation in a cGAS-dependent manner. Moreover, pharmacological inhibition of GSDMD-mediated Pyroptosis and PD-L1 improve anti-tumor immunity, highlighting the potential of combining GSDMD/PD-L1 inhibition for immunotherapy as a therapeutic strategy.

Keywords

CP: Cancer; CP: Immunology; GSDMD; anti-tumor immunity; macrophage/DC.

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