Research ArticleCancer

Improved Survival with T Cell Clonotype Stability After Anti–CTLA-4 Treatment in Cancer Patients

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Science Translational Medicine  28 May 2014:
Vol. 6, Issue 238, pp. 238ra70
DOI: 10.1126/scitranslmed.3008211

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Cancer’s Glass Jaw

In the body’s bout against cancer, antibodies that block CTLA-4 (cytotoxic T lymphocyte–associated antigen-4) induce the immune system to enter the ring. But precisely how these antibodies affect the broad tumor-restricted T cell response remains unclear. Now, Cha et al. use next-generation sequencing to show that blocking CTLA-4 in cancer sufferers drives turnover of the T cell repertoire. However, increasing T cell diversity is not the whole story—patients with more favorable clinical outcomes maintained certain high-frequency T cells with treatment, whereas patients who lost T cells prevalent before therapy had poorer prognosis. These data suggest that although CTLA-4 blockade induces T cell repertoire diversification, maintenance of high-frequency—and presumably high-avidity—clones may be relevant for the antitumor immune response.

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