Immunology

A Weapon of Mass Distraction

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Science  07 Nov 2003:
Vol. 302, Issue 5647, pp. 951
DOI: 10.1126/science.302.5647.951b

Tumors can be slippery customers when it comes to their recognition and destruction by the immune system. Often this is because the similarity of tumor cells to their healthy counterparts makes detection by tumor-reactive T cells difficult. Uyttenhove et al. uncover a further means by which tumors may actively thwart the efforts of T cells. In a large panel of human tumors, many expressed the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO). T cells are particularly sensitive to tryptophan availability, meaning that IDO is able to inhibit both mouse and human T cell proliferation. In a mouse model, where T cell immunity normally leads to a rapid rejection of tumors, rejection did not occur when tumor cells were engineered to express IDO, and an IDO inhibitor partially restored tumor rejection. Thus, by depleting the local tryptophan pool, tumors may divert, en masse, the unwanted attention of T cells. — SJS

Nature Med. 9, 1269 (2003).

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