CCR2-dependent recruitment of Tregs and monocytes following radiotherapy is associated with TNFa-mediated resistance

Michele Mondini, Pierre Louis Loyher, Pauline Hamon, Marine Gerbe de Thore, Marie Laviron, Kevin Berthelot, Celine Clemenson, Benoit L. Salomon, Christophe Combadiere, Eric Deutsch, Alexandre Boissonnas

Research output: Contribution to journalArticlepeer-review

92 Scopus citations

Abstract

Radiotherapy (RT) represents one of the main anti-accumulation of tumor necrosis factor alpha (TNFa)-pro-cancer approaches for the treatment of solid tumors. ducing monocytes and CCR2 þ regulatory T cells (Treg). Beyond the expected direct effects of RT on tumor cells, This corecruitment was associated with a TNFa-dependent evidence supporting the importance of an immune activation of Tregs, dampening the efficacy of RT. Our response to RT is growing. The balance between RT-medi-results highlight an unexpected cross-talk between innate ated immunogenic and tolerogenic activity is ill-defined and adaptive immune system components and indicate and deserves more attention. Herein, a murine model of CCL2/CCR2 and TNFa as potential clinical candidates to head and neck squamous cell carcinoma was used to counterbalance the radioprotective action of monocyte-demonstrate that RT upregulated CCL2 chemokine pro-derived cells and Tregs, paving the way for potent com-duction in tumor cells, leading to a CCR2-dependent bined radioimmunotherapies.

Original languageEnglish
Pages (from-to)376-387
Number of pages12
JournalCancer Immunology Research
Volume7
Issue number3
DOIs
StatePublished - Mar 2019
Externally publishedYes

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