Correlation Between Immune Microenvironment And Therapeutic Efficacy In Head And Neck Squmaous Cancer

Background: Head and neck squmaous cancer(HNSCC)ranks seventh in global cancer incidence.On the basis of traditional treatments including surgical resection and chemoradiation,the prognosis of HNSCC remains poor.The tumor microenvironment(TME)is significantly associated with clinical outcomes and therapeutic efficacy.However,the landscape of the HNSCC microenvironment is not fully understood.Therefore,we divided HNSCC into three classes according to differences in the TME to determine effective personalized treatments.Methods: We explored the immune landscape of head and neck cancer by analysing the gene expression profile of 501 cases from the Cancer Genome Atlas(TCGA)data Portal.The levels of immune components in the tumor microenvironment were evaluated via single-sample gene set enrichment(ss GSEA)analysis.According to different immune scores,we used k-means clustering to divide these patients into three groups.The survival analysis was performed using the Kaplan-Meier method and log-rank test.The independent prognostic variables were defined based on the results of univariate and multivariate Cox analyses.Hub genes were identified with the protein-protein interaction network for the DEGs.We validated the prognostic role of key gene in cases from the Gene Expression Omnibus(GEO)database and the First Hospital of China Medical University.Results: The HNSCC were clustered into an Immunity-H group(n=264),Immunity-M group(n=185)and Immunity-L group(n=52)according to 40 immune components in the tumor microenvironment.DNA damage and HLA genes play an important role in immune regulation.The patients in the Immunity-H group had a favourable survival compared with patients in the Immunity-M group and the Immunity-L group.The patients in the Immunity-H group and Immunity-M group could benefit from radiotherapy.In addition,the Immunity-L group showed the lowest PD-1 expression,PD-L1 expression,CTLA-4 expression and immunophenoscore,and had poor response to anti-PD-1 treatment.CXCR3 was demonstrated to be downregulated in the Immunity-L group,which was related to shorter OS in the TCGA and GEO databases,suggesting CXCR3 as a potential therapeutic target.Conlusion: Taken together,our findings proposed three new microenvironment-related phenotypes of HNSCC with different prognosis and therapy efficacy and suggested that CXCR3 played a major role in immune regulation and could be a novel therapeutic target,providing a reference for clinical decisions and research directions in the future.