Evidence is accumulating that an inflammatory T-cell infiltrate and preexisting tumor-specific T-cell response are a prerequisite for a favorable outcome of immunotherapy as well as to conventional therapeutic interventions.31, 32 Because of the increased expression of OX40, as well as CTLA-4 and PD-1 in the TIL of SCCHN patients shown in this investigation, we hypothesize that modulating these pathways will be therapeutically beneficial in both the HPV-positive and -negative populations. The gene discussed is TNFRSF4; the disease is head and neck squamous cell carcinoma.