Activation of the VEGFC/VEGFR3 pathway induces tumor immune escape in colorectal cancer.
Fiche publication
Date publication
juin 2019
Journal
Cancer research
Auteurs
Membres identifiés du Cancéropôle Est :
Pr PEYRIN-BIROULET Laurent
Tous les auteurs :
Tacconi C, Ungaro F, Correale C, Arena V, Massimino L, Detmar M, Spinelli A, Carvello M, Mazzone M, Oliveira AI, Rubbino F, Garlatti V, Spanò S, Lugli E, Colombo FS, Malesci A, Peyrin-Biroulet L, Vetrano S, Danese S, D'Alessio S
Lien Pubmed
Résumé
Colorectal cancer (CRC) is a major cause of cancer-related death in Western countries and is associated with increased numbers of lymphatic vessels (LVs) and tumor-associated macrophages (TAMs). The VEGFC/VEGFR3 pathway is regarded as the principal inducer of lymphangiogenesis and it contributes to metastases; however, no data are available regarding its role during primary CRC development. We found that both VEGFC and VEGFR3 were upregulated in human non-metastatic CRC, with VEGFR3 expressed on both LVs and TAMs. With the use of three different preclinical models of CRC, we also discovered that the VEGFC/VEGFR3 axis can shape both lymphatic endothelial cells (LECs) and TAMs to synergistically inhibit anti-tumor immunity and promote primary CRC growth. Therefore, VEGFR3-directed therapy could be envisioned for the treatment of non-metastatic CRC.
Référence
Cancer Res.. 2019 Jun 25;: