Research ArticleCancer

Up-Regulation of PD-L1, IDO, and Tregs in the Melanoma Tumor Microenvironment Is Driven by CD8+ T Cells

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Science Translational Medicine  28 Aug 2013:
Vol. 5, Issue 200, pp. 200ra116
DOI: 10.1126/scitranslmed.3006504

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The Great Escape

One of the long-standing questions in cancer biology is how tumors evade the patrolling immune response. Many potential explanations have been proposed, including that the tumor itself suppresses the immune response. Indeed, some of the most promising new immunotherapies work by blocking inhibitory molecules, which enhances immune activity against the tumor. Now, Spranger et al. show that immunosuppressive mechanisms in the tumor may involve negative feedback loops dependent on an infiltrating immune response.

The authors noticed that even tumors that are infiltrated with CD8+ T cells are not rejected and that this correlated with expression of three types of immunosuppressives: indoleamine-2,3-dioxygenase (IDO), PD-L1/B7-H1, and regulatory T cells. Mechanistic studies in mice suggested that CD8+ T cells were required to be in the tumor microenvironment for the up-regulation of these immunosuppressives. Extending these studies to the clinic, patients with inflammatory tumor infiltrates will thus be more likely to benefit from immune checkpoint therapies.