CCR2 and head and neck squamous cell carcinoma: Taken together, these findings provide compelling evidence that within the immunosuppressive TME, the impact of the IL6/IL6R and CCL2/CCR2 signaling on the ability of HPV − tumors to evade immune attack by NK cells is more pronounced than their impact on HPV + tumors, and dual blockade of these two pathways is more effective to potentiate the antitumor activity of NK cells in HPV − HNSCC cells (Fig. 8).