The Immunological Impact of Chemotherapy on the Tumor Microenvironment of Oral Squamous Cell Carcinoma

　Anticancer drugs induce cell-cycle arrest and apoptosis not only in tumor cells, but also in immune cells. However, many preclinical and clinical findings show that some chemotherapeutic agents can improve the antitumor efficacy of immunotherapy. We immunohistochemically analyzed the degree of immune cell infiltration and the relevance of programmed cell death 1 ligand-1 (PD-L1) expression in surgically resected oral squamous cell carcinoma (OSCC) specimens from patients who had undergone pretreatment with certain chemotherapies and other patients without pretreatment. We divided the patients into the group of neoadjuvant chemotherapy (NAC) patients (n=8) and the nNAC (without NAC) patient group (n=10). We observed that NAC induced infiltrations of CD4, CD8 T cells and CD56 NK cells into the tumor microenvironment. Decreased numbers of Tregs and PD-1-positive cells were observed in the NAC group. No significant difference was observed in the degree of immune-cell infiltration between the patient groups except for CD56 NK cells in the stroma and PD-1 cells in cancer nests. Eighty percent of the nNAC specimens showed intermediate-to-strong PD-L1 protein expression, whereas 75% of the NAC specimens showed down-regulation of the PD-L1 protein, indicating the effectiveness of the chemotherapeutic treatment before surgery.