美国哈佛医学院Vijay K. Kuchroo团队在研究中取得进展。他们发现靶向肽聚糖识别蛋白1（PGLYRP1）促进抗肿瘤免疫同时抑制自身免疫性神经炎症。这一研究成果发表在2023年10月12日出版的国际学术期刊《自然-免疫学》上。

研究表明编码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潜在靶点。小鼠Pglyrp1缺失导致CD8⁺ T细胞中肿瘤生长减少和激活/效应表型增加，表明CD8⁺ T细胞中PGLYRP1发挥抑制功能。令人惊讶的是，Pglyrp1缺失阻碍实验性自身免疫性脑脊髓炎的进展，这是中枢神经系统自身免疫性疾病的一种模型。PGLYRP1缺陷的髓系细胞在抗原呈递和T细胞活化方面存在缺陷，表明PGLYRP1可能在自身免疫期间的骨髓细胞中发挥促炎分子的作用。

这些结果表明PGLYRP1是免疫治疗的一个潜在靶点，作为免疫靶点引起有效的抗肿瘤免疫反应，同时防止某些组织炎症和自身免疫。

据介绍，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，从而使T细胞功能失调。虽然免疫检查点阻断是成功治疗多种人类癌症的选择，但严重的自身免疫样不良反应会限制其应用。

附：英文原文

Title: Targeting PGLYRP1 promotes antitumor immunity while inhibiting autoimmune neuroinflammation

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

Issue&Volume: 2023-10-12

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.

DOI: 10.1038/s41590-023-01645-4

Source: https://www.nature.com/articles/s41590-023-01645-4