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

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Title:	Influence of tumor-associated macrophages and HLA class I expression according to HPV status in head and neck cancer patients receiving chemo/bioradiotherapy.
Authors:	Ou, Dan¹ (AUTHOR), Adam, Julien¹ (AUTHOR), Garberis, Ingrid¹ (AUTHOR), Blanchard, Pierre¹ (AUTHOR), Nguyen, France¹ (AUTHOR), Levy, Antonin¹ (AUTHOR), Casiraghi, Odile¹ (AUTHOR), Gorphe, Philippe¹ (AUTHOR), Breuskin, Ingrid¹ (AUTHOR), Janot, François¹ (AUTHOR), Temam, Stephane¹ (AUTHOR), Scoazec, Jean-Yves¹ (AUTHOR), Deutsch, Eric¹ (AUTHOR), Tao, Yungan¹ (AUTHOR) yungan.tao@gustaveroussy.fr
Source:	Radiotherapy & Oncology. Jan2019, Vol. 130, p89-96. 8p.
Subjects:	Head & neck cancer, Cancer patients, Subgroup analysis (Experimental design), Squamous cell carcinoma
Abstract:	Highlights • 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. Abstract 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. [ABSTRACT FROM AUTHOR]
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Database:	Engineering Source

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Abstract:	Highlights • 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. Abstract 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. [ABSTRACT FROM AUTHOR]
ISSN:	01678140
DOI:	10.1016/j.radonc.2018.08.013