Correlate the TP53 Mutation and the HRAS Mutation with Immune Signatures in Head and Neck Squamous Cell Cancer

Abstract

Although immunotherapy has emerged as an effective therapeutic strategy for various cancers including head and neck squamous cell carcinomas (HNSCCs), only a subset of patients can benefit from such therapy. Hence, it is pressing to discover predictive biomarkers for cancer immunotherapy response. <i>TP53</i> and <i>HRAS</i> mutations frequently occur in HNSCC and correlate with a worse prognosis in HNSCC. We extensively characterized the associations of <i>TP53</i> mutations and <i>HRAS</i> mutations with HNSCC immunity based on multiple cancer genomics datasets. We compared the enrichment levels of 20 immune signatures between <i>TP53</i>-mutated and <i>TP53</i>-wildtype HNSCCs, and between <i>HRAS</i>-mutated and <i>HRAS</i>-wildtype HNSCCs, and found that <i>TP53</i> mutations were associated with depressed immune signatures while <i>HRAS</i> mutations were associated with enhanced immune signatures in HNSCC. Moreover, we found multiple p53- and RAS-mediated pathways showing significant correlations with HNSCC immunity. Furthermore, we demonstrated that the association between <i>TP53</i> mutation and tumor immunity was independent of the human papillomavirus (HPV) infection and smoking status in HNSCC. These data suggest that p53 and RAS may play important roles in regulating HNSCC immunity and that the <i>TP53</i> and <i>HRAS</i> mutation status could be useful biomarkers for stratifying HNSCC patients responsive to immunotherapy.