Human Tumor Immunology
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Group Leader Pierre Coulie Sophie Lucas Contact Pierre Coulie and Sophie Lucas de Duve Institute and Université catholique de Louvain GECE - B1.74.04, Avenue Hippocrate 74, B-1200 Brussels phone (direct) : 32 (0)2 764 75 81 fax : 32 (0)2 764 75 90 e-mail: Pierre Coulie Sophie Lucas Group members > |
Research topics
Vaccination of cancer patients with defined tumor antigens recognized by T lymphocytes is followed by objective tumor regression in a minority of patients. Our goal is to understand the mechanisms of these tumor regressions and the reasons for their rarity.
1. Immune responses to cancer vaccine antigens: We have developed very sensitive methods for the detection of blood CD8+ T lymphocytes recognizing defined combinations of HLA class I molecules and antigenic peptides. Applying these methods to vaccinated cancer patients, we made the unexpected observation that the anti-vaccine T cell responses were often of a very low level, even in those patients who displayed tumor regression following vaccination.
2. In situ analysis of tumor-infiltrating T lymphocytes: We and others have observed that tumor-specific T cells could be present within human tumors. The reasons for this seemingly pacific co-existence of tumor cells and tumor-specific T lymphocytes remain unclear, even though a few mechanisms have been elucidated in vitro or in animal models. Our goal is to analyse human tumor-infiltrating T cells in situ, using a combination of histochemistry, microdissection, and gene expression analysis.
3. Regulatory T cells: Analysis of anti-tumor immune responses in cancer patients indicates that the rarity of clinical responses after vaccination may be due to intra-tumoral inhibition of immune effectors. We are investigating whether regulatory T lymphocytes, or Tregs, are implicated in this local immune suppression. To this aim, we have developed tools to quantify Tregs in human tissues, and are attempting to decipher the molecular mechanisms that underlay their suppressive function. We are currently focusing on TGFß, an immunosuppressive cytokine which we have shown to be produced by human T reg clones.
