Triggering the resolution of inflammation with agonistic anti-ChemR23 antibody dampens inflammation-driven carcinogenesis and metastasis - Archive ouverte HAL Access content directly
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Triggering the resolution of inflammation with agonistic anti-ChemR23 antibody dampens inflammation-driven carcinogenesis and metastasis

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Abstract

Triggering the resolution of inflammation with agonistic anti-ChemR23 antibody dampens inflammation-driven carcinogenesis and metastasis Chronic inflammation is associated with abnormal non-phlogistic clearance (efferocytosis) of apoptotic cells by macrophages and a defect of the resolution of inflammation pathways. The resolution of inflammation is an active immunological process mediated by specialized pro-resolving mediator (SPM) which target specific resolutive G-protein coupled receptors expressed by different immune cells and participate at the return to tissue homeostasis after an injury. Defects in the clearance of (chemotherapy-induced) apoptotic tumor cell debris strengthens inflammation and has been associated with exacerbated tumor growth in several preclinical models. Proresolutive therapeutic approaches, such as using exogenous resolvin E1 (RvE1), the natural lipidic proresolutive ligand of GPCR ChemR23, have been shown to dampen tumor-associated inflammation and to reduce tumor growth. We found that ChemR23 is inducible on myeloid cells by inflammatory stimuli and mainly expressed by tumor associated macrophages in melanoma and lung cancers. We identified an agonist anti-ChemR23 mAb that accelerates the resolution of inflammation in acute inflammatory model in mice. Finally, we report that agonist anti-ChemR23 mAb limits chronic inflammation in the tumor microenvironment and inhibits metastasis development.
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Dates and versions

inserm-03349406 , version 1 (20-09-2021)

Identifiers

  • HAL Id : inserm-03349406 , version 1

Cite

Vanessa Gauttier, Margot Lavy, Charlène Trilleaud, Kévin Biteau, Stéphanie Neyton, et al.. Triggering the resolution of inflammation with agonistic anti-ChemR23 antibody dampens inflammation-driven carcinogenesis and metastasis. American Association for Cancer Researc 2021, 2021, Virtual Meeting, United States. ⟨inserm-03349406⟩
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