Intriguingly, HPV+ and HPV− HNSCC possess molecularly distinct landscapes and subsequently variability in clinical outcome.42 It has been reported that HPV+ tissues, in comparison to HPV− or adjacent cancer-free tissues, have significantly higher expression of LAG3, PD-1, TIGIT, and TIM3.42 Utilizing the HPV16 E6 and E7 expressing cell line, TC1, we observed significant antitumor activity with αTIGIT + bintrafusp alfa combination therapy (Figure 6b), associated with the appreciable increase in CD45+ cells, CD8+ T cells, NK cells, M-MDSCs, and DCs (Figure 6c). This evidence concerns the gene CD8A and head and neck squamous cell carcinoma.