Laboratory of Immunoregulation and Inflammation, Institut Pasteur de Montevideo, Montevideo, Uruguay.
Immunobiology Department, Faculty of Medicine, University of the Republic, Montevideo, Uruguay.
Clin Exp Immunol. 2020 May;200(2):155-162. doi: 10.1111/cei.13433.
Immune checkpoint blockers improve the overall survival of a limited number of patients among different cancers. Identifying pathways that influence the immunological and clinical response to treatment is critical to improve the therapeutic efficacy and predict clinical responses. Recently, a key role has been assigned to innate immune mechanisms in checkpoint blockade-driven anti-tumor responses. However, inflammatory pathways can both improve and impair anti-tumor immunity. In this review, we discuss how different inflammatory pathways, particularly inflammasome activation, can influence the clinical outcome of immune checkpoint blockers. Inflammasome activation may reinforce anti-tumor immunity by boosting CD8 T cell priming as well as by enhancing T helper type 17 (Th17) responses. In particular, we focus on the modulation of the cation channel transmembrane protein 176B (TMEM176B) and the ectonucleotidase CD39 as potential targets to unleash inflammasome activation leading to reinforced anti-tumor immunity and improved efficacy of immune checkpoint blockers. Future studies should be aimed at investigating the mechanisms and cell subsets involved in inflammasome-driven anti-tumor responses.
免疫检查点抑制剂可改善多种癌症患者的总体生存率。确定影响治疗免疫和临床反应的途径对于提高治疗效果和预测临床反应至关重要。最近，先天免疫机制在检查点阻断驱动的抗肿瘤反应中发挥了关键作用。然而，炎症途径既可以改善也可以损害抗肿瘤免疫。在这篇综述中，我们讨论了不同的炎症途径，特别是炎症小体激活，如何影响免疫检查点抑制剂的临床疗效。炎症小体的激活可以通过增强 CD8 T 细胞的启动以及增强辅助性 T 细胞 17（Th17）反应来增强抗肿瘤免疫。特别是，我们专注于阳离子通道跨膜蛋白 176B（TMEM176B）和核苷酸酶 CD39 的调节，作为潜在的靶点，以释放炎症小体激活，从而增强抗肿瘤免疫并提高免疫检查点抑制剂的疗效。未来的研究应旨在研究炎症小体驱动的抗肿瘤反应中涉及的机制和细胞亚群。
