Targeting PGLYRP1 promotes antitumor immunity while inhibiting autoimmune neuroinflammation

Alexandra Schnell, Linglin Huang, Brianna M.L. Regan, Vasundhara Singh, Dominik Vonficht, Alina Bollhagen, Mona Wang, Yu Hou, Lloyd Bod, Raymond A. Sobel, Norio Chihara, Asaf Madi, Ana C. Anderson, Aviv Regev, Vijay K. Kuchroo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Co-inhibitory and checkpoint molecules suppress T cell function in the tumor microenvironment, thereby rendering T cells dysfunctional. Although immune checkpoint blockade is a successful treatment option for multiple human cancers, severe autoimmune-like adverse effects can limit its application. Here, we show that the gene encoding peptidoglycan recognition protein 1 (PGLYRP1) is highly coexpressed with genes encoding co-inhibitory molecules, indicating that it might be a promising target for cancer immunotherapy. 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, genetic deletion of Pglyrp1 protected against the development of experimental autoimmune encephalomyelitis, a model of autoimmune disease in the central nervous system. PGLYRP1-deficient myeloid cells had a defect in antigen presentation and T cell activation, indicating that PGLYRP1 might function as a proinflammatory molecule in myeloid cells during autoimmunity. These 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.

Original languageEnglish
Pages (from-to)1908-1920
Number of pages13
JournalNature Immunology
Volume24
Issue number11
DOIs
StatePublished - Nov 2023

Funding

FundersFunder number
German Academic Scholarship Foundation
National Institutes of HealthR01CA187975, P01AI039671, P01AI073748, P01AI056299, R01AI144166
Studienstiftung des Deutschen Volkes

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