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Background    IL27  has been reported to play dual roles in cancer; however, its effects on the tumor microenvironment (TME), immunotherapy, and prognosis in melanoma remain largely unclear. This study was aimed to uncover the effects of  IL27  on TME, immunotherapy and prognosis in patients with melanoma.    Methods  RNA-seq data, drug sensitivity data, and clinical data were obtained from TCGA, GEO, CCLE, and CTRP. Log-rank test was used to determine the survival value of  IL27 . Univariate and multivariate Cox regression analyses were employed to determine the independent predictors of survival outcomes. DAVID and GSEA were used to perform gene set functional annotations. ssGSEA was used to explore the association between  IL27  and immune infiltrates. ConsensusClusterPlus was used to classify melanoma tissues into hot tumors or cold tumors.    Results  Clinically,  IL27  was negatively correlated with Breslow depth ( P  = 0.00042) and positively associated with response to radiotherapy ( P  = 0.038). High  IL27  expression showed an improved survival outcome ( P  = 0.00016), and could serve as an independent predictor of survival outcomes (hazard ratio: 0.32 - 0.88,  P  = 0.015). Functionally, elevated  IL27  expression could induce an enhanced immune response and pyroptosis ( R  = 0.64,  P  = 1.2e-55), autophagy ( R  = 0.37,  P  = 7.1e-17) and apoptosis ( R  = 0.47,  P  = 1.1e-27) in patients with melanoma. Mechanistically, elevated  IL27  expression was positively correlated with cytotoxic cytokines (including  INFG  and  GZMB ), enhanced immune infiltrates, and elevated CD8/Treg ratio ( R  = 0.14,  P  = 0.02), possibly driving CD8 +  T cell infiltration by suppressing β-catenin signaling in the TME. Furthermore,  IL27  was significantly associated with hot tumor state, multiple predictors of response to immunotherapy, and improved drug response in patients with melanoma.    Conclusions    IL27  was correlated with enriched CD8 +  T cells, desirable therapeutic response and improved prognosis. It thus can be utilized as a promising modulator in the development of cytokine-based immunotherapy for melanoma.

Integrative Characterization of the Role of IL27 In Melanoma Using Bioinformatics Analysis