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

• Published in: Radiotherapy and oncology Vol. 130; pp. 89 - 96
• Main Authors: Ou, Dan, Adam, Julien, Garberis, Ingrid, Blanchard, Pierre, Nguyen, France, Levy, Antonin, Casiraghi, Odile, Gorphe, Philippe, Breuskin, Ingrid, Janot, François, Temam, Stephane, Scoazec, Jean-Yves, Deutsch, Eric, Tao, Yungan
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.01.2019; Elsevier
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cetuximab; Chemoradiotherapy; Chemoradiotherapy - adverse effects; Female; Head and neck cancers; Head and Neck Neoplasms - immunology; Head and Neck Neoplasms - mortality; Head and Neck Neoplasms - therapy; Head and Neck Neoplasms - virology; Histocompatibility Antigens Class I - analysis; HLA class I; Human papillomavirus; Humans; Life Sciences; Macrophages - physiology; Male; Middle Aged; Papillomaviridae - isolation & purification; Papillomavirus Infections; Prognosis; Squamous Cell Carcinoma of Head and Neck - immunology; Squamous Cell Carcinoma of Head and Neck - mortality; Squamous Cell Carcinoma of Head and Neck - therapy; Squamous Cell Carcinoma of Head and Neck - virology; Tumor-associated macrophage; HLA class I; Human papillomavirus; Head and neck cancers; Tumor-associated macrophage; Cetuximab; Chemoradiotherapy
• ISSN: 0167-8140; 1879-0887
• DOI: 10.1016/j.radonc.2018.08.013

•Intraepithelial macrophage density was associated with favorable progression-free survival.•HLA class I down-regulation was not an independent prognostic factor.•Stromal M2 density may potentially be used to guide treatment selection. 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). 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. 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). The prognostic role of TAM phenotype and distribution depends on HPV status and might predict treatment response. They prompt further validation in prospective studies.