共抑制分子和检查点分子抑制肿瘤微环境中的 T 细胞功能，从而导致 T 细胞功能障碍。尽管免疫检查点阻断是多种人类癌症的成功治疗选择，但严重的自身免疫样副作用可能限制其应用。在这里，我们发现编码肽聚糖识别蛋白1（PGLYRP1）的基因与编码共抑制分子的基因高度共表达，表明它可能是癌症免疫治疗的一个有前途的靶点。小鼠中 Pglyrp1 的基因缺失导致肿瘤生长减少，CD8 T 细胞中的激活/效应表型增加，表明 PGLYRP1 在 CD8 T 细胞中具有抑制功能。令人惊讶的是，Pglyrp1 的基因缺失可以防止实验性自身免疫性脑脊髓炎（一种中枢神经系统自身免疫性疾病模型）的发展。 PGLYRP1缺陷的骨髓细胞在抗原呈递和T细胞激活方面存在缺陷，表明PGLYRP1可能在自身免疫过程中充当骨髓细胞中的促炎分子。这些结果凸显 PGLYRP1 作为免疫治疗的一个有前途的靶点，当靶向时，会引发有效的抗肿瘤免疫反应，同时防止某些形式的组织炎症和自身免疫。© 2023。作者，获得 Springer Nature America, Inc 的独家许可。

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.© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.