Sun Runzi, Gao David Shihong, Shoush Jason, Lu Binfeng
Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Semin Cancer Biol. 2022 Nov;86(Pt 2):280-295. doi: 10.1016/j.semcancer.2022.05.002. Epub 2022 May 14.
The IL-1 family of cytokines consists of IL-1α, IL-1β, IL-18, IL-33, IL-36α, IL-36β, and IL-36γ. These proteins form four signaling receptor complexes: the IL-1 receptor (IL-1R1 and IL-1RAcP), the IL-18 receptor (IL-18Rα and IL-18Rβ), the IL-33 receptor (ST2 and IL-1RAcP), and the IL-36 receptor (IL-1Rrp2 and IL-1RAcP). The formation of receptor complexes is also regulated by various antagonistic molecules and decoy receptors. The IL-1 family cytokines are induced and secreted by both innate immune cells and tissue cells upon infection and tissue damage. Thus, they play a diverse role in mediating both innate and adaptive immune responses. During tumor development and cancer treatment, the expression of the IL-1 gene family is differentially regulated in tumor cells, tissue stromal cells, and immune cells in a stage specific and tissue specific manner. Like other cytokines, the IL-1 family proteins have pleiotropic functions that are dependent on diverse arrays of target cells. As a result, they play a complex role in tumorigenesis, cancer metastasis, immune suppression, and cancer immune surveillance. Here, we focus on reviewing experimental evidence demonstrating how members of the IL-1 family influence cancer development at the cellular and molecular level. The unique mechanisms of this group of cytokines make them attractive targets for new cancer therapy.
白细胞介素 -1（IL-1）细胞因子家族由IL-1α、IL-1β、IL-18、IL-33、IL-36α、IL-36β和IL-36γ组成。这些蛋白质形成四种信号受体复合物：IL-1受体（IL-1R1和IL-1RAcP）、IL-18受体（IL-18Rα和IL-18Rβ）、IL-33受体（ST2和IL-1RAcP）以及IL-36受体（IL-1Rrp2和IL-1RAcP）。受体复合物的形成也受到各种拮抗分子和诱饵受体的调节。IL-1家族细胞因子在感染和组织损伤时由先天免疫细胞和组织细胞诱导并分泌。因此，它们在介导先天免疫和适应性免疫反应中发挥着多种作用。在肿瘤发生发展和癌症治疗过程中，IL-1基因家族的表达在肿瘤细胞、组织基质细胞和免疫细胞中以阶段特异性和组织特异性的方式受到差异调节。与其他细胞因子一样，IL-1家族蛋白具有多效性功能，这取决于多种靶细胞。因此，它们在肿瘤发生、癌症转移、免疫抑制和癌症免疫监视中发挥着复杂的作用。在此，我们着重综述实验证据，以证明IL-1家族成员如何在细胞和分子水平上影响癌症发展。这组细胞因子的独特机制使其成为新型癌症治疗的有吸引力的靶点。
