| First Author | Jiang Y | Year | 2022 |
| Journal | Cell Rep | Volume | 41 |
| Issue | 4 | Pages | 111553 |
| PubMed ID | 36288704 | Mgi Jnum | J:330610 |
| Mgi Id | MGI:7380197 | Doi | 10.1016/j.celrep.2022.111553 |
| Citation | Jiang Y, et al. (2022) Gasdermin D restricts anti-tumor immunity during PD-L1 checkpoint blockade. Cell Rep 41(4):111553 |
| abstractText | 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. |
