Dan Ou1, Julien Adam2, Ingrid Garberis3, Pierre Blanchard4, France Nguyen4, Antonin Levy5, Odile Casiraghi2, Philippe Gorphe6, Ingrid Breuskin6, François Janot6, Stephane Temam6, Jean-Yves Scoazec7, Eric Deutsch5, Yungan Tao8. 1. Department of Radiation Oncology, Gustave Roussy Cancer Campus, Villejuif, France; Université Paris Sud, France; INSERM1030 Molecular Radiotherapy, Villejuif, France; Department of Radiation Oncology, Fudan University Shanghai Cancer Center, China; Department of Oncology, Shanghai Medical College, Fudan University, China. 2. Department of Pathology, Gustave Roussy Cancer Campus, Villejuif, France. 3. Department of Pathology, Gustave Roussy Cancer Campus, Villejuif, France; INSERM US23/CNRS UMS3655, Molecular Analysis, Modelling and Imaging of Cancer Disease, Experimental and Translational Pathology, Villejuif, France. 4. Department of Radiation Oncology, Gustave Roussy Cancer Campus, Villejuif, France. 5. Department of Radiation Oncology, Gustave Roussy Cancer Campus, Villejuif, France; Université Paris Sud, France; INSERM1030 Molecular Radiotherapy, Villejuif, France. 6. Department of Head and Neck Oncology, Gustave Roussy Cancer Campus, Villejuif, France. 7. Université Paris Sud, France; Department of Pathology, Gustave Roussy Cancer Campus, Villejuif, France; INSERM US23/CNRS UMS3655, Molecular Analysis, Modelling and Imaging of Cancer Disease, Experimental and Translational Pathology, Villejuif, France. 8. Department of Radiation Oncology, Gustave Roussy Cancer Campus, Villejuif, France; Université Paris Sud, France; INSERM1030 Molecular Radiotherapy, Villejuif, France. Electronic address: yungan.tao@gustaveroussy.fr.
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.
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 cancerpatients (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.
Authors: Saskia J Santegoets; Chantal L Duurland; Ekaterina J Jordanova; Vanessa J van Ham; Ilina Ehsan; Nikki M Loof; Vipin Narang; Charles A Dutertre; Florent Ginhoux; Sylvia L van Egmond; Marij J P Welters; Sjoerd H van der Burg Journal: J Immunother Cancer Date: 2020-08 Impact factor: 13.751
Authors: Barbora Pokrývková; Jana Šmahelová; Natálie Dalewská; Marek Grega; Ondřej Vencálek; Michal Šmahel; Jaroslav Nunvář; Jan Klozar; Ruth Tachezy Journal: Diagnostics (Basel) Date: 2021-03-31