The high expression of immune checkpoint co-stimulators predicts a favorable prognosis in head and neck carcinomas

Abstract Objectives: T cells require second immune checkpoint molecules for activation and immune memory after antigen presentation. In our previous study, we found ICOS a favorable prognostic factor amongst B7 immune checkpoint co-stimulators (ICSs) families in head and neck squamous cell carcinoma (HNSCC) and oral SCC (OSCC). Materials and method: This study analyzed the expression of on-B7 TNF ligand/receptor superfamily ICSs in the Cancer Genome Atlas (TCGA) HNSCC cohort, our OSCC cohort, and pan-cancer datasets. The correlation in expression, prognosis, and immune status was assessed. Results: The higher expression of CD27, CD30, CD40L, DR3, and OX40, presumably on the T cell surface, defined better overall survival of HNSCC patients. Besides, CD27, CD30, CD40L, and OX40 were highly correlated with ICOS expression in tumors. CD27, CD40L, and DR3 expression are higher in HPV+ HNSCC tumors than in HPV- tumors. The combined expression level of CD27/OX40 or CD27/CD40L/OX40 enables the potent survival prediction of small, less nodal involvement, early stage, and HPV+ tumor subsets. In both HNSCC and our OSCC cohorts, tumors expressing high CD27, CD30, CD40L, ICOS, and OX40 exhibited enhanced immune cell infiltration. The high correlation in the expression of these ICSs is also noted in the vast majority of tumor types in addition to HNSCC in TCGA datasets. Conclusion: The findings suggest that the concordant stimulation of CD27, CD30, CD40L, ICOS, and OX40 could be a crucial strategy in cancer immunotherapy.