Schnell, AlexandraHuang, LinglinRegan, BriannaVonficht, DominikBollhagen, AlinaWang, MonaHou, YuBod, LloydChihara, NorioMadi, AsafAnderson, AnaKuchroo, Vijay2023-12-142023-10-12Schnell, Alexandra, Linglin Huang, Brianna Regan, Dominik Vonficht, Alina Bollhagen, Mona Wang, Yu Hou et al. "Targeting PGLYRP1 promotes antitumor immunity while inhibiting autoimmune neuroinflammation." Nat Immunol 24, no. 11 (2023): 1908-1920. DOI: 10.1038/s41590-023-01645-41529-29081529-2916https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37377516Co-inhibitory and checkpoint molecules suppress T-cell function in the tumor microenvironment, thereby rendering T cells dysfunctional. While immune checkpoint blockade (ICB) has emerged as a successful treatment option for multiple human cancers, severe autoimmune-like side effects limit its application. Here we found the gene encoding the Peptidoglycan Recognition Protein 1 (PGLYRP1) to be highly co-expressed with co-inhibitory molecules and hypothesized that it might be a promising target for cancer immunotherapy. Indeed, genetic deletion of PGLYRP1 in mice led to decreased tumor growth and an increased activation/effector phenotype in CD8+ T cells, suggesting an inhibitory function of PGLYRP1 in CD8+ T cells. Surprisingly, the genetic deletion of PGLYRP1 strongly protected against the development of experimental autoimmune encephalomyelitis (EAE), a model of autoimmune disease in the central nervous system (CNS). Pglyrp1-deficient myeloid cells had a defect in antigen presentation and T-cell activation, indicating that PGLYRP1 might act as a proinflammatory molecule in myeloid cells during autoimmunity. Our results highlight PGLYRP1 as a promising target for immunotherapy that, when targeted, elicits a potent antitumor immune response while protecting against some forms of tissue inflammation and autoimmunity.en-USImmunologyImmunology and AllergyJournal Article2023-12-1410.1038/s41590-023-01645-4