To evaluate whether blockade of CXCR1/2 receptors could impact responses to chemotherapy in HNSCC, here we used SX-682, a clinical stage, dual small-molecule inhibitor of CXCR1 and CXCR2 that was previously shown with multiple preclinical tumor models to decrease the migration of immune suppressive, CXCR2-positive PMN-MDSC from the periphery into the tumor, leading to improved tumor control [9, 10, 12, 38]. Here, CXCR1 is linked to head and neck squamous cell carcinoma.