Association of Suppressive Myeloid Cell Enrichment with Aggressive Oropharynx Squamous Cell Carcinoma

SIMPLE SUMMARY: Human papillomavirus positive (HPV+) ororpharyngeal squamous cell carcinoma (OPSCC) patients have improved clinical prognosis, compared to HPV-negative OPSCC patients. While HPV+ OPSCC patients often have more immune-cell-infiltrated tumors, they can be subjected to increased immunoregulatory influence. The purpose of this study was to examine the tumor immune microenvironment, via mRNA expression profiling, in patients with OPSCC, focusing primarily on HPV+ patients with aggressive disease (patients with known recurrent or metastatic disease). Using primary-patient pre-treatment tumor tissue samples, we demonstrated that HPV-negative and aggressive-HPV+ OPSCC patients have increased monocyte/macrophage and granulocyte progenitor cell enrichment. We examined The Cancer Genome Atlas (TCGA) database for head and neck cancer to find similar trends in myeloid cell enrichment in more aggressive OPSCC. ABSTRACT: Background: While immune-cell infiltrated tumors, such as human papillomavirus positive (HPV+) ororpharyngeal squamous cell carcinomas (OPSCC) have been associated with an improved clinical prognosis, there is evidence to suggest that OPSCCs are also subjected to increased immunoregulatory influence. The objective of this study was to assess whether patients with clinically aggressive OPSCC have a distinct immunosuppressive immune signature in the primary tumor. Methods: This retrospective case-control study analyzed 37 pre-treatment tissue samples from HPV+ and HPV-negative OPSCC patients treated at a single institution. The cases were patients with known disease recurrence and the controls were patients without disease recurrence. An mRNA-expression immune-pathway profiling was performed, and correlated to clinical outcomes. The TCGA head and neck cancer database was utilized to make comparisons with the institutional cohort. Results: In our cohort, HPV-negative and HPV+ patients with known disease recurrence both had significantly increased suppressive monoctyte/macrophage and granulocyte cell-expression-profile enrichment. Similar findings were found in the TCGA cohort when comparing HPV-negative to positive patients. Conclusions: our study demonstrates that patients with recurrent HPV+ OPSCC had suppressive monocyte/macrophage and granulocyte immune-cell enrichment, similar to those seen in the more aggressive HPV-negative OPSCC.