Invited Lecture: Tumoral immune resistance resulting from constitutive expression of indoleamine 2,3-dioxygenase by tumor cells
(2007) 1st European IDO Meeting. Andreas Hermes Akademie — Location: Bonn, Germany (18.April.2007)
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- Abstract
- Immunotherapy based on therapeutic vaccination of cancer patients is a promising new approach for cancer therapy. It is based on a thorough understanding of the antigens expressed by cancer cells and the nature of the immune response that can be raised against them. These antigens correspond to peptides presented at the cell surface by MHC class I molecules. Clinical trials of cancer vaccines indicate that this approach is not toxic and leads to significant clinical benefit in a minority of patients. However, it appears that an important factor limiting the efficacy of immunotherapy in non-responsive patients is the development of mechanisms allowing tumors to resist or escape immune rejection. It is therefore critical to identify such mechanisms and design therapeutic approaches able to overcome it. A powerful tumor resistance mechanism is based on the expression by tumor cells of Indoleamine 2,3-dioxygenase (IDO), an intracellular enzyme that catalyses rapid tryptophan degradation, resulting in a local tryptophan depletion that severely affects T lymphocyte proliferation and is thereby profoundly immunosuppressive. We showed that many human tumors express IDO in a constitutive manner. We confirmed that tumoral IDO was enzymatically active. Making use of a preclinical model system, we also showed that this constitutive expression of IDO endows tumor cells with the ability to resist immune rejection by preventing T cell attack in vivo. Importantly, this effect was partly reverted by systemic treatment of mice with 1-methyl-L-tryptophan, an inhibitor of IDO. These results suggest that the efficacy of therapeutic vaccination of cancer patients could be improved by concomitant administration of an IDO inhibitor. Uyttenhove, C., L. Pilotte, I. Theate, V. Stroobant, D. Colau, N. Parmentier, T. Boon, and B.J. Van den Eynde. 2003. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat. Med. 9:1269-74.
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Van den Eynde, B. (2007). Invited Lecture: Tumoral immune resistance resulting from constitutive expression of indoleamine 2,3-dioxygenase by tumor cells. 1st European IDO Meeting. Andreas Hermes Akademie, Bonn, Germany. https://hdl.handle.net/2078.5/48273