Research ArticleCancer

MHC Class I–Associated Phosphopeptides Are the Targets of Memory-like Immunity in Leukemia

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Science Translational Medicine  18 Sep 2013:
Vol. 5, Issue 203, pp. 203ra125
DOI: 10.1126/scitranslmed.3006061

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Adding to the Toolkit for Cancer Therapy

The immune system is increasingly being used as a tool for cancer therapy. Researchers have harnessed the body’s own defense system to specifically target tumors. However, one limitation of immune-targeting strategies is the relative lack of targets. Because cancer cells are derived from normal human tissue, ideal antigens would be specifically or differentially expressed by tumor cells and healthy tissues. Now, Cobbold et al. find that phosphoproteins may broaden the pool of tumor antigens that can be targeted with immunotherapy.

One difference between cancer and normal cells is the way in which they are regulated. Indeed, signal transduction pathways are frequently dysregulated in cancer cells. The authors now use a hallmark of signal transduction—protein phosphorylation—to identify and characterize new phosphoantigens that stimulate immune cells. They identified 95 phosphopeptides presented on the surface of leukemic cells and demonstrated that they could be recognized and killed by phosphopeptide-specific cytotoxic T lymphocytes. Somewhat surprisingly, healthy individuals had high levels of responses to phosphopeptides, but these responses were muted in leukemia patients with poor prognosis. What’s more, allogeneic stem cell transplant could restore phosphoprotein immune response in patients. These data suggest that phosphopeptides could be developed as new targets for cancer immunotherapy.

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