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. Here, FOXP3 is linked to neoplasm.