Dynamic changes in immune cell profile in head and neck squamous cell carcinoma: Immunomodulatory effects of chemotherapy

Tumor cells have evolved sophisticated means of escape from the host immune system. To date, several important immunological phenomena have been revealed in peripheral blood as well as within tumors. In the present study, we first investigated the proportion and activation status of peripheral immune regulatory cells and CD8(+) T-cell subsets in patients with head and neck squamous cell carcinoma (HNSCC) using a multicolor flow cytometer, and then evaluated how therapy with docetaxel, cisplatin, and 5-fluorouracil modulated the immune cell profile in peripheral blood. The proportion of naïve T cells was lower and that of effector memory T cells (TEM ) was higher in HNSCC patients than in healthy donors. Moreover, the proportions of activated TEM cells and effector T cells (TEFF ) were dramatically increased in patients with advanced stage disease. The proportion of regulatory T cells and CD14(+) HLA-DR(-) myeloid-derived suppressor cells was elevated in HNSCC patients. Of note, after therapy, in addition to the transient reduction in immune regulatory cells, decreases in central memory T cells and increases in TEFF cells were observed among CD8(+) T-cell subsets, suggesting differentiation from central memory T cells into TEFF cells. Our results suggested that, despite the immunosuppressive status in HNSCC patients, tumor-specific immune responses mediated by CD8(+) T cells might be induced and maintained. Moreover, chemotherapy can trigger not only a transient reduction in immune regulatory cells but also further activation of CD8(+) T cells.