van der Bruggen, Pierre

The analysis of the T cell responses of melanoma patients vaccinated against tumor antigens has led us to consider the possibility that the limiting factor for therapeutic success is not the intensity of the anti-vaccine response but the degree of anergy presented by intratumoral lymphocytes. We try to understand why tumor-infiltrating lymphocytes are unable to kill tumor cells, and to find strategies to overcome this blockage. We have discovered a new type of anergy of human tumor-infiltrating lymphocytes, due to the presence of galectin-3, a lectin abundant in tumors, as it is corrected by galectin antagonists. We are analyzing the mechanisms by which galectin antagonists reverse the impaired function and we look for agents that correct this function.

Models available:

  • Carcinoma ascites of patients, human blood samples, human T cell clones

Cells available:

  • Main focus on MDSC's and T cells

Technology available:

Research in man. Human studies are focused on T-cell dysfunctions

Key publications related to Mye-EUNITER:

  1. Demotte N., Bigirimana R., Wieërs G., Stroobant V., Squifflet J.-L., Carrasco J., Thielemans K., Baurain J.-F., Van Der Smissen P., Courtoy P.J., and van der Bruggen P.  A short treatment with galactomannan GM-CT-01 corrects the functions of freshly isolated human tumor-infiltrating lymphocytes.  Clinical Cancer Research, 20 : 1823-1833, 2014. (IF  8.193)

  2. Antonopoulos A., Demotte N., Stroobant V., Haslam S.M., van der Bruggen P., and Dell A. Loss of effector function of human cytolytic T lymphocytes is accompanied by major alterations in N- and O-glycosylation.  Journal of Biological Chemistry, 287 : 11240-11251, 2012. (IF: 4.651)

  3. Demotte N., Wieërs G., Van Der Smissen P., Moser M., Schmidt C.W., Thielemans K., Squifflet J.-L., Weynand B., Carrasco J., Lurquin C., Courtoy P.J., and van der Bruggen P. A galectin-3 ligand corrects the impaired function of human CD4 and CD8 tumor-infiltrating lymphocytes and favors tumor rejection in mice.  Cancer Research, 70 : 7476-7488, 2010. (IF: 8.234)

  4. François V., Ottaviani S., Renkvist N., Stockis J., Schuler G., Thielemans K., Colau D., Marchand M., Boon T., Lucas S., and van der Bruggen P. The CD4+ T-cell response of melanoma patients to a MAGE-A3 peptide vaccine involves potential regulatory T cells.  Cancer Research, 69 : 4335-4345, 2009. (IF: 7.543)

  5. Demotte N., Stroobant V., Courtoy P.J., Van Der Smissen P., Colau D., Luescher I.F., Hivroz C., Nicaise J., Squifflet J.-L., Mourad M., Godelaine D., Boon T., and van der Bruggen P. Restoring the association of the T cell receptor with CD8 reverses anergy in human tumor-infiltrating lymphocytes.  Immunity, 28 : 414-424, 2008. (IF: 20.579)