CD4 and neoplasm: Differences in TME content of CD8+ T cells (e.g., exhaustion states) and regulatory immune cells (e.g., Foxp3+ CD4+ Tregs and myeloid-derived suppressor cells) as well as differences in T cell trafficking to the tumor and tumor-intrinsic immune suppression all serve as potential mechanisms underlying the divergence in immune cell interactions and responses to immunotherapy operating in the TME of HNSCC that should be therapeutically targeted.