IL27, an interleukin, has diverse influences on the immune response. Initially linked to Th1 responses, it is now recognized as a regulator of inflammation, modifying T cell functions, inducing IL-10, and promoting T regulatory cell responses. It is part of the interleukin-12 family, with shared receptor and cytokine subunits influencing cancer, infection, and inflammatory diseases [2,3].

In hepatocellular carcinoma (HCC), IL27R signaling promotes tumor development. High IL27EBI3 cytokine or IL27RA expression correlates with poor prognosis. Loss of IL27R suppresses HCC in two different in-vivo hepatocarcinogenesis models. Mechanistically, IL27R signaling restrains the cytotoxicity of innate cytotoxic lymphocytes in the tumor microenvironment. Pharmacologic neutralization of IL27 signaling reduces HCC development [1]. In melanoma, high IL27 expression is associated with an improved survival outcome, enhanced immune response, and may drive CD8+ T cell infiltration by suppressing β-catenin signaling in the tumor microenvironment [4].

In summary, IL27 plays a significant role in regulating the immune response and is involved in cancer development. Studies using gene knockout models, like the loss of IL27R in HCC models, have revealed its tumor-promoting role in specific diseases. Understanding IL27's function can provide potential therapeutic targets for diseases such as HCC and melanoma.

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. Tait Wojno, Elia D, Hunter, Christopher A, Stumhofer, Jason S. . The Immunobiology of the Interleukin-12 Family: Room for Discovery. In Immunity, 50, 851-870. doi:10.1016/j.immuni.2019.03.011. https://pubmed.ncbi.nlm.nih.gov/30995503/

4. 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/