Two studies have uncovered genetic determinants that shape the response of patients with melanoma to anti-cytotoxic T lymphocyte associated antigen 4 (CTLA4) therapy. Using whole-genome sequencing, these studies identified recurrent mutations that could predict response. Riaz et al. found that mutations in SERPINB3 and SERPINB4 were associated with survival following anti-CTLA4 therapy. By contrast, Gao et al. reported that mutations in interferon-γ (IFNγ) pathway genes correlated with primary resistance to CTLA4 blockade. These findings underline the importance of accurate patient selection for responses to immune checkpoint blockade.
References
Gao, J. et al. Loss of IFN-γ pathway genes in tumor cells as a mechanism of resistance to anti-CTLA-4 therapy. Cell 167, 397–404 (2016)
Riaz, N. et al. Recurrent SERPINB3 and SERPINB4 mutations in patients who respond to anti-CTLA4 immunotherapy. Nat. Genet. http://dx.doi.org/10.1038/ng.3677 (2016)
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Dart, A. Checkpoint barriers. Nat Rev Cancer 16, 678 (2016). https://doi.org/10.1038/nrc.2016.118
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DOI: https://doi.org/10.1038/nrc.2016.118
