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Genetic diversity of tumors with mismatch repair deficiency influences anti–PD-1 immunotherapy response

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Science  03 May 2019:
Vol. 364, Issue 6439, pp. 485-491
DOI: 10.1126/science.aau0447

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High mutational load gets a response

Cancers harbor many genetic mutations. Defects in DNA mismatch repair prevent tumors from repairing certain types of DNA damage and lead to a hypermutable genomic state known as microsatellite instability (MSI). Some tumors with a high degree of MSI may be treatable with PD-1 (programmed cell death–1) immunotherapy, but patient response is highly variable. Mandal et al. studied drivers of differential response to immunotherapy in these patients and found that MSI intensity and insertion-deletion mutations strongly affected therapeutic outcome.

Science, this issue p. 485

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