Critical immunotherapy target marks dysfunctional regulatory T cells in brain cancer


Immunotherapy represents an exciting advance in cancer treatment that harnesses the immune system to seek and destroy cancer cells. The programmed death 1 (PD-1) pathway dampens immune responses to tumor cells, and several clinical trials have shown favorable outcomes by targeting PD-1 or its ligand PD-1L. In this issue of JCI Insight, David Hafler and colleagues at Yale University and Massachusetts Institute of Technology examined PD-1-expressing regulatory T cells in glioblastoma multiforme, an extremely aggressive form of brain cancer. Regulatory T cells normally constrain immune responses and keep other types of T cells from mounting hyper-aggressive responses. Although anti-PD1 therapy is generally thought to promote conventional T cell activity, the Hafler team now reports that PD-1 expression on regulatory T cells from the tumors of glioblastoma multiforme patients correlates with regulatory T cell dysfunction. They also found that glioblastoma multiforme patients treated with a PD-1 blocking antibody had a higher proportion of dysfunctional regulatory T cells. These observations suggest the possibility that PD-1 targeting therapies could work, in part, by driving further regulatory T cell dysfunction. Future studies will be needed to more fully understand the contribution of this pathway to anti-tumor effects.


TITLE: PD-1 marks dysfunctional regulatory T cells in malignant gliomas

Yale School of Medicine
Email: [email protected]

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JCI Insight is the newest publication from the American Society of Clinical Investigation, a nonprofit honor organization of physician-scientists. JCI Insight is dedicated to publishing a range of translational biomedical research with an emphasis on rigorous experimental methods and data reporting. All articles published in JCI Insight are freely available at the time of publication. For more information about JCI Insight and all of the latest articles go to

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