IL13-Mediated Dectin-1 and Mannose Receptor Overexpression Promotes Macrophage Antitumor Activities through Recognition of Sialylated Tumor Cells

Mohammad Alaeddine (1) , Mélissa Prat (1) , Verena Poinsot (2) , Valérie Gouazé-Andersson (1) , Hélène Authier (1) , Etienne Meunier (1) , Lise Lefèvre (1) , Camille Alric (1) , Christophe Dardenne (1) , José Bernad (1) , Laurent Alric (1) , Bruno Ségui (3) , Patricia Balard (4) , François Couderc (2, 5) , Bettina Couderc (3) , Bernard Pipy (1) , Agnès Coste (1)

1 PHARMA-DEV - Pharmacochimie et Biologie pour le Développement
2 IMRCP - Interactions moléculaires et réactivité chimique et photochimique
3 CRCT - Centre de Recherches en Cancérologie de Toulouse
4 Laboratoire Nutergia
5 IMRCP - BIBAC - IMRCP - Chimie analytique et interactions biomolécules - matière molle biomimétique

Macrophage-mediated cytotoxicity is controlled by surface receptor expression and activation. Despite the numerous studies documenting the role of macrophage C-type lectin receptors (CLR) in pathogen elimination, little is known about their contribution to antitumor responses. Here, we report that IL13 inhibits T-cell lymphoma and ovarian adenocarcinoma development in tumor-bearing mice through the conversion of tumor-supporting macrophages to cytotoxic effectors, characterized by a CLR signature composed of dectin-1 and mannose receptor (MR). We show that dectin-1 and MR are critical for the recognition of tumor cells through sialic acid-specific glycan structure on their surface and for the subsequent activation of macrophage tumoricidal response. Finally, we validated that IL13 antitumor effect mediated by dectin-1 and MR overexpression on macrophages can extend to various types of human tumors. Therefore, these results identify these CLRs as potential targets to promote macrophage antitumor response and represent an attractive approach to elicit tumor-associated macrophage tumoricidal properties.

Mots clés: Animals; Arginase / metabolism; Cell Line; Tumor; Gene Expression; Humans; Interleukin-13 / genetics; Interleukin-13 / metabolism; Lectins; C-Type / genetics; C-Type / metabolism; Macrophages / immunology; Macrophages / metabolism; Mannose-Binding Lectins / genetics; Mannose-Binding Lectins / metabolism; Mice; Mice Knockout; N-Acetylneuraminic Acid / metabolism; Necrosis / genetics; Necrosis / immunology; Neoplasms / etiology; Neoplasms / metabolism; Neoplasms / mortality; Neoplasms / pathology; Prognosis; Reactive Oxygen Species / metabolism; Receptors; Cell Surface / genetics; Cell Surface / metabolism; Signal Transduction; T-Lymphocytes / immunology; T-Lymphocytes / metabolism

Domaines: Chimie

Mohammad Alaeddine, Mélissa Prat, Verena Poinsot, Valérie Gouazé-Andersson, Hélène Authier, et al.. IL13-Mediated Dectin-1 and Mannose Receptor Overexpression Promotes Macrophage Antitumor Activities through Recognition of Sialylated Tumor Cells. Cancer Immunology Research, 2019, ⟨10.1158/2326-6066.CIR-18-0213⟩. ⟨hal-02194445⟩