par Jean-Philippe Girard, directeur de l’Institut de Pharmacologie et de biologie structurale, CNRS-Université de Toulouse

à 11h45 (nouvel horaire), en Salle de conférences de la Plateforme Génomique Fonctionnelle – site de Carreire zone Sud, Université de Bordeaux

dans le cadre de la série de conférences mensuelles « Concepts in Cancer » organisée par Andreas Bikfalvi – Inserm U1029 et les conférences FR TransBioMed

Blood vessels and tumor angiogenesis are generally associated with tumor growth and poor clinical outcome of cancer patients. However, we discovered that some blood vessels present within the tumor microenvironment can be associated with favorable prognosis by contributing to tumor suppression rather than tumor growth (Martinet, … and Girard, Cancer Res 2011). These specialized blood vessels, designated high endothelial venules (HEVs), are normally found in lymph nodes where they mediate lymphocyte entry from the blood (Girard et al., Nat Rev Immunol 2012). A high density of tumor-associated HEVs in human breast carcinomas and melanomas was associated with high levels of cytotoxic lymphocyte infiltration, indicating that HEVs may participate in the eradication of tumors by facilitating access of ‘killer’ lymphocytes into tumor tissues. Therefore, the type of blood vessels found in the tumor microenvironment is critical for clinical outcome, and increasing the density of the ‘good’ HEV blood vessels within solid tumors represents a promising novel strategy for cancer therapy. In contrast, in hematological cancers (lymphomas, leukemias), HEV blood vessels may contribute to the resistance to chemotherapy by facilitating the entry of leukemic cells in lymph nodes (Lafouresse, … and Girard, Blood 2015). It may therefore be necessary to interfere with the function of HEV blood vessels in hematological cancers. It is thus important to better characterize HEV blood vessels at the molecular level and to define the mechanisms involved in their regulation. These mechanisms are still poorly understood, despite our results indicating a critical role for dendritic cells in the process (Moussion and Girard, Nature 2011).

The role of HEV blood vessels in cancer (both solid tumors and hematological cancer) will be presented in this seminar. Our recent data on the characterization of HEV blood vessels by single cell RNA-Seq, intravital microscopy and multiphoton in vivo imaging, and the influence of tumor-associated HEVs on the response to cancer therapeutics will be discussed.

References :     

1) Moussion C and Girard JP. Dendritic cells control lymphocyte entry into lymph nodes via high endothelial venules. Nature, 2011, 479:542-546

2) Martinet L*, Garrido I*,  Filleron T, Le Guellec S,  Bellard E, Fournie JJ, Rochaix P and Girard JP. Human solid tumors contain high endothelial venules (HEVs): association with T and B lymphocyte infiltration and favorable prognosis in breast cancer. Cancer Res, 2011, 71:5678-5687

3) Girard JP*, Moussion C and Forster R. HEVs, lymphatics and homeostatic immune cell trafficking in lymph nodes. Nature Rev Immunol, 2012, 12:762-773 (*Corresponding author)

4) Lafouresse F, Bellard E, Laurent C, Moussion C, Fournié JJ, Ysebaert L and Girard JP. L-selectin controls trafficking of chronic lymphocytic leukemia cells in lymph node high endothelial venules in vivo. Blood, 2015, 126:1336-1345 (This article has been selected by the Editors for the cover of the journal and a research highlight in “Inside Blood” 2015, 126:1267-1268)