Influence of tumor-associated macrophages and HLA class I expression according to HPV status in head and neck cancer patients receiving chemo/bioradiotherapy

Background and purpose: To investigate the prognostic value of tumor-associated macrophages (TAM) and HLA class I expression according to HPV status in patients with head and neck squamous cell carcinoma treated with definitive radiotherapy combining cisplatin (CRT) or cetuximab (BRT). Material and methods: Ninety-five patients were enrolled. The density of CD68+ cells and CD68+ CD163+ cells (further referred as M2) in the intraepithelial and the stromal compartments, respectively, as well as HLA class I expression in tumor cells, were evaluated semi-quantitatively. Correlations between biomarker expression and treatment outcomes were analyzed. Results: Multivariate analysis showed that the intraepithelial macrophage density (IEMD) was prognostic for favorable progression-free survival (PFS) and there was a non-significant trend for improved overall survival (OS). HLA class I down-regulation was not an independent prognostic factor. Subgroup analysis showed that in p16+ population, patients with high IEMD had improved 5-year PFS vs. patients with low IEMD (81.2% vs. 25.0%, p < 0.001), while in p16- population, no difference was observed. Similarly, when stratified by primary tumor site, IEMD showed prognostic value in oropharyngeal cancer patients (OPC) but not non-OPC patients. Five-year PFS of patients with low stromal M2 macrophage density treated with CRT was significantly improved vs. those with BRT (54.5% vs. 36.1%, p = 0.03), while in tumors with high M2, there was no significant difference (50.3% vs. 42.9%, p = 0.67). Conclusions: The prognostic role of TAM phenotype and distribution depends on HPV status and might predict treatment response. They prompt further validation in prospective studies. (C) 2018 Elsevier B.V. All rights reserved.