Regulation of T Lymphocyte Function in Tumors group

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Pierre van der Bruggen, Member

Daniele GODELAINE, Senior Investigator
Flavia CALMON-HAMATY, Postdoctoral Fellow
Nathalie DEMOTTE, Postdoctoral Fellow
Monica GORDON-ALONSO, Postdoctoral Fellow
Claude WILDMANN, Research Associate
Anne-Elisabeth PETIT, PhD Student
Eva JACOBS, Technician
Vinh HA THI, Technician
Nathalie KRACK, Secretary

P van der Bruggen

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The analysis of the T cell responses of melanoma patients vaccinated against tumor antigens has led 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, apparently due to the presence of galectin-3, a lectin abundant in tumors, as it is corrected by galectin ligands. We are further analyzing the mechanisms by which galectin ligands reverse the impaired function and we look for agents that correct this function. We intend to set up clinical trials combining anti-tumoral therapeutic vaccination and injection of galectin ligands.

Selected publications

  1. A galectin-3 ligand corrects the impaired function of human CD4 and CD8 tumor-infiltrating lymphocytes and favors tumor rejection in mice. Demotte N, Wieërs G, Van Der Smissen P, Moser M, Schmidt CW, Thielemans K, Squifflet J-L, Weynand B, Carrasco J, Lurquin C, Courtoy PJ, van der Bruggen P. Cancer Res. 2010 , 70:7476-88
  2. Restoring the association of the T cell receptor with CD8 reverses anergy in human tumor-infiltrating lymphocytes. 
Demotte N, Stroobant V, Courtoy PJ, Van Der Smissen P, Colau D, Luescher IF, Hivroz C, Nicaise J, Squifflet JL, Mourad M, Godelaine D, Boon T, van der Bruggen P. 
Immunity. 2008, 28:414-24
  3. Vaccination of a Melanoma Patient with Mature Dendritic Cells Pulsed with MAGE-3 Peptides Triggers the Activity of Nonvaccine Anti-Tumor Cells. 
Carrasco J, Van Pel A, Neyns B, Lethé B, Brasseur F, Renkvist N, van der Bruggen P, van Baren N, Paulus R, Thielemans K, Boon T, Godelaine D. 
J Immunol. 2008, 180:3585-93
  4. CD45RA on human CD8 T cells is sensitive to the time elapsed since the last antigenic stimulation. 
Carrasco J, Godelaine D, Van Pel A, Boon T, van der Bruggen P. 
Blood. 2006, 108:2897-905
  5. Human T cell responses against melanoma.
Boon T, Coulie PG, Van den Eynde BJ, van der Bruggen P. 
Annu Rev Immunol. 2006;24:175-208. Review.
  6. A polyclonal anti-vaccine CD4 T cell response detected with HLA-DP4 multimers in a melanoma patient vaccinated with MAGE-3.DP4-peptide-pulsed dendritic cells. 
Zhang Y, Renkvist N, Sun Z, Schuler-Thurner B, Glaichenhaus N, Schuler G, Boon T, van der Bruggen P, Colau D. 
Eur J Immunol. 2005, 35:1066-75
  7. Tumor-specific shared antigenic peptides recognized by human T cells. 
Van Der Bruggen P, Zhang Y, Chaux P, Stroobant V, Panichelli C, Schultz ES, Chapiro J, Van Den Eynde BJ, Brasseur F, Boon T. 
Immunol Rev. 2002, 188:51-64
  8. A reversible functional defect of CD8+ T lymphocytes involving loss of tetramer labeling. 
Demotte N, Colau D, Ottaviani S, Godelaine D, Van Pel A, Boon T, van der Bruggen P. 
Eur J Immunol. 2002, 32:1688-97
  9. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. 
van der Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, Van den Eynde B, Knuth A, Boon T. 
Science. 1991, 254:1643-7