CD8A and head and neck squamous cell carcinoma: In a transgenic HNSCC mouse model, anti-TIM-3 monoclonal antibody injection induced a reduction in Tregs and increased IFN-γ production on CD8+ T cells, suggesting that the antitumor immune response was enhanced by TIM-3 blockade through relieved suppression of negative immune factors.40 Therefore, increased Tregs and upregulated inhibitory receptors on TCF1−Texterm might construct an immunosuppressive microenvironment in the TIME, resulting in a barrier to the efficacy of immunotherapy.