Effects of PRKCH on CD8+T cell function and melanoma immunotherapy

Abstract

Objective To explore the effect of PRKCH on CD8+T cell function and its role in predicting the efficacy of melanoma immunotherapy. Methods Kaplan-Meier survival analysis was used to evaluate the correlation between PRKCH and overall survival (OS) in melanoma immunotherapy cohorts and The Cancer Genome Atlas (TCGA) data. Single-cell RNA-sequencing (scRNA-seq) data were employed to analyze the cellular expression of PRKCH. Protein-protein interaction (PPI) networks and gene set enrichment analysis (GSEA) were applied to analyze the mechanism of PRKCH-induced anti-tumor immune responses. After retroviral overexpression and knockdown of PRKCH, the function of mouse CD8+T cells was examined. The anti-tumor effect of PRKCH overexpressed OT-1 CD8+T cells was assessed using B16-OVA mouse melanoma model. Results A positive correlation was observed between PRKCH expression and OS in the melanoma ICI cohorts and SKCM data in TCGA. scRNA-seq data indicated that PRKCH was expressed in T cells. PPI, GSEA and scRNA-seq data showed that PRKCH may induce more cytotoxic and memory T cells. PRKCH overexpression and knockdown enhanced and decreased CD8+T cell proliferation and IFN-γ and Granzyme B expression, respectively. Additionally, PRKCH overexpression enhanced the tumor inhibition of OT-1 CD8+T cells. Conclusion PRKCH enhances the anti-tumor effect of CD8+T cells, and can be used to predict the efficacy of immunotherapy in melanoma.

Keywords

• prkch
• melanoma
• immunotherapy
• tumor microenvironment
• cd8+t cells