Persistent Mutation Burden Drives Sustained Anti-Tumor Immune Responses

Study ID Alternative Stable ID Type
EGAS00001006660 Other

Study Description

Tumor mutation burden is an imperfect proxy of tumor foreignness and has therefore failed to consistently demonstrate clinical utility in predicting responses in the context of immunotherapy. We evaluated mutations in regions of the genome that are unlikely to undergo loss and discovered that clonal mutations in single-copy regions and those present in multiple copies per cell constitute a persistent tumor mutation burden (pTMB) that is linked with therapeutic response to immune checkpoint blockade. Persistent mutations were retained in the context of tumor evolution under selective pressure of immunotherapy and tumors with a high pTMB content were characterized by a more inflamed tumor microenvironment. pTMB imposes an evolutionary bottleneck that cancer cells cannot overcome and may thus drive sustained immunologic tumor control in the context of immunotherapy.

Study Datasets 1 dataset.

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Dataset ID Description Technology Samples
Data includes whole exome sequenced bam files for matched tumor-normal pairs from the study.
Illumina HiSeq 2500 90

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