Research ArticleCancer

Integrated molecular analysis of tumor biopsies on sequential CTLA-4 and PD-1 blockade reveals markers of response and resistance

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Science Translational Medicine  01 Mar 2017:
Vol. 9, Issue 379, eaah3560
DOI: 10.1126/scitranslmed.aah3560

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Checking on checkpoint inhibitors

Immune checkpoint blockade has greatly improved the success of treatment in melanoma and other tumor types, but it is expensive and does not work for all patients. To optimize the likelihood of therapeutic success and reduce the risks and expense of unnecessary treatment, it would be helpful to find biomarkers that can predict treatment response. Roh et al. studied patients treated with sequential checkpoint inhibitors targeting CTLA-4 and then PD-1. In these patients, the authors discovered that a more clonal T cell population specifically correlates with response to PD-1 blockade, but not CTLA-4, which may help identify the best candidates for this treatment. In addition, increased frequency of gene copy number loss was correlated with decreased responsiveness to either therapy.

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