Figure 6. Head and neck squamous cell carcinoma (HNSCC) immune landscape and implications for immunotherapy.

(A) HNSCC tumors possess the highest median Treg infiltration and the highest Treg/CD8⁺ T cell infiltration ratio of the 10 most immune-infiltrated tumors, providing a strong rationale to target modulators of Treg function such as CTLA-4, GITR, ICOS, IDO, VEGFA, and others in head and neck cancer immunotherapy. (B) HNSCC tumors possess the highest median CD56^dim NK cell infiltration of the 10 most immune-infiltrated tumors providing, an additional rationale to augment NK cell activity in head and neck cancer via modulation of suppressive and agonistic receptors found on NK cells such as KIR, PD-1, TIGIT, 4-1BB, and others. (C) Patients displaying molecular smoking signatures possessed lower immune infiltration of their tumors and displayed worse survival, suggesting these patients may benefit from immune stimulatory therapy such as IL-2, TLR, and STING agonists. Green arrows indicate stimulatory signals and red arrows indicated inhibitory signals.