Il27, interleukin-27, is a cytokine with diverse influences on the immune response. It was initially linked to Th1 responses, but now is recognized as a modulator of T cell effector functions, inducer of IL-10, and promoter of T regulatory cell responses. It is involved in multiple biological processes, especially those related to immunity, metabolism, and cancer [2].

In hepatocellular carcinoma (HCC), loss-of-function experiments in two different models of hepatocarcinogenesis showed that loss of Il27R suppressed HCC in vivo. Il27R signaling within the tumor microenvironment restrains the cytotoxicity of innate cytotoxic lymphocytes, and its ablation enhanced their accumulation and activation [1]. In melanoma, high Il27 expression was associated with improved survival, and it may drive CD8+ T cell infiltration by suppressing β-catenin signaling in the tumor microenvironment [3].

In conclusion, Il27 plays crucial roles in immunity and cancer. Gene knockout or conditional knockout mouse models have revealed its function in promoting HCC development by regulating innate cytotoxic lymphocytes, and its potential beneficial role in melanoma prognosis. These findings suggest its potential as a therapeutic target in these diseases [1,3].

References:

1. Aghayev, Turan, Mazitova, Aleksandra M, Fang, Jennifer R, Grivennikov, Sergei I, Koltsova, Ekaterina K. . IL27 Signaling Serves as an Immunologic Checkpoint for Innate Cytotoxic Cells to Promote Hepatocellular Carcinoma. In Cancer discovery, 12, 1960-1983. doi:10.1158/2159-8290.CD-20-1628. https://pubmed.ncbi.nlm.nih.gov/35723626/

2. Yoshida, Hiroki, Hunter, Christopher A. . The immunobiology of interleukin-27. In Annual review of immunology, 33, 417-43. doi:10.1146/annurev-immunol-032414-112134. https://pubmed.ncbi.nlm.nih.gov/25861977/

3. Dong, Chunyu, Dang, Dan, Zhao, Xuesong, Wang, Zhijun, Zhang, Chuan. 2021. Integrative Characterization of the Role of IL27 In Melanoma Using Bioinformatics Analysis. In Frontiers in immunology, 12, 713001. doi:10.3389/fimmu.2021.713001. https://pubmed.ncbi.nlm.nih.gov/34733272/