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.
TP53
and
HRAS
mutations frequently occur in HNSCC and correlate with a worse prognosis in HNSCC. We extensively characterized the associations of
TP53
mutations and
HRAS
mutations with HNSCC immunity based on multiple cancer genomics datasets. We compared the enrichment levels of 20 immune signatures between
TP53
-mutated and
TP53
-wildtype HNSCCs, and between
HRAS
-mutated and
HRAS
-wildtype HNSCCs, and found that
TP53
mutations were associated with depressed immune signatures while
HRAS
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
TP53
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
TP53
and
HRAS
mutation status could be useful biomarkers for stratifying HNSCC patients responsive to immunotherapy.
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