In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 5668-5668
Abstract:
Local radiotherapy is the major treatment to control locally advanced head and neck cancer. Evidence supporting the importance of immune response in the response to radiation therapy is growing and the possibility to potentiate the effects of radiotherapy by modulating the function of the immune system offers new exciting therapeutic perspectives. Preclinical findings suggest that immunomodulatory agents may synergize with radiotherapy, increasing local response rates and inducing sustained systemic responses. The role of monocytes/macrophages in the response to radiotherapy is under extensive investigation. Among the many cytokines secreted by tumor cells, CCL2 is involved in inflammatory monocyte recruitment from bone marrow to the inflammatory site. We have recently developed a model of human papillomavirus (HPV)-related head and neck cancer using immunocompetent mice and validated its usefulness to evaluate the tumor response to radiotherapy. Using the same model, based on the injection of TC1/luciferase cells in the inner lip of C57Bl/6 mice, we show that local radiotherapy induces an increase of CCL2 levels in the bloodstream and intratumorally accompanied by a neo-infiltration of monocytes in the tumor that subsequently differentiate into tumor-associated macrophages (TAM). When TC1/Luc cells were engrafted in CCL2-/- or CCR2-/- mice, the tumor response to radiotherapy and survival were improved. This was accompanied by an impaired infiltration of inflammatory monocytes, and a subsequent decrease of TAM levels at later time points. In vitro, exposure to ionizing radiation increased the secretion of CCL2 by TC1/Luc cells, and such increase was significantly enhanced when tumor cells were co-cultured with irradiated RAW 264.7 macrophage-derived cells. This data suggests interplay between tumor and TAM that can amplify the effects of radiotherapy on the immune system. We propose that reducing radiation-induced monocyte recruitment may yield improved results in the treatment of HPV-related head and neck squamous cell carcinomas by radiotherapy. Immunologically-augmented radiotherapy could allow reduction of the delivered radiation dose, thus minimizing the risk of treatment sequelae while maintaining optimal tumor control. Citation Format: Michele Mondini, Pierre L. Loyher, Kevin Berthelot, Céline Clémenson, Alexandre Boissonnas, Eric Deutsch. CCL2/CCR2-driven monocyte recruitment to the tumor following radiotherapy influences the outcome of the treatment of head and neck cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5668. doi:10.1158/1538-7445.AM2017-5668
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2017-5668
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2017
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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