HPV-associated head and neck cancer is characterized by distinct profiles of CD8 T cells and myeloid-derived suppressor cells.

Patients with HPV-localized head and neck cancer (HNC) show inferior outcomes after surgery and radiochemotherapy compared to HPV-associated cancers. The underlying mechanisms remain elusive, but differences in immune status and immune activity may be implicated. In this study, we analyzed immune profiles of CD8 T cells and myeloid-derived suppressor cells (MDSC) in HPV versus HPV disease.The overall frequency of CD8 T cells was reduced in HNC versus healthy donors but substantially increased after curative therapy (surgery and/or radiochemotherapy). In HPV patients, this increase was associated with significant induction of peripheral blood CD8/CD45RA/CD62L effector memory cells. The frequency of HPV-antigen-specific CD8 cells was low even in patients with virally associated tumors and dropped to background levels after curative therapy. Pre-therapeutic counts of circulating monocytic MDSC, but not PMN-MDSC, were increased in patients with HPV disease. This increase was accompanied by reduced fractions of terminally differentiated CD8 effector cells. HPV tumors showed reduced infiltrates of CD8 and CD45RO immune cells compared with HPV tumors. Importantly, frequencies of tumor tissue-infiltrating PMN-MDSC were increased, while percentages of Granzyme B and Ki-67 CD8 T cells were reduced in patients with HPV disease.We report differences in frequencies and relative ratios of MDSC and effector T cells in HPV HNC compared with more immunogenic HPV-associated disease. Our data provide new insight into the immunological profiles of these two tumor entities and may be utilized for more tailored immunotherapeutic approaches in the future.