{"doi":"10.1126/science.aan6733","title":"Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade","abstract":"The genomes of cancers deficient in mismatch repair contain exceptionally high numbers of somatic mutations. In a proof-of-concept study, we previously showed that colorectal cancers with mismatch repair deficiency were sensitive to immune checkpoint blockade with antibodies to programmed death receptor-1 (PD-1). We have now expanded this study to evaluate the efficacy of PD-1 blockade in patients with advanced mismatch repair-deficient cancers across 12 different tumor types. Objective radiographic responses were observed in 53% of patients, and complete responses were achieved in 21% of patients. Responses were durable, with median progression-free survival and overall survival still not reached. Functional analysis in a responding patient demonstrated rapid in vivo expansion of neoantigen-specific T cell clones that were reactive to mutant neopeptides found in the tumor. These data support the hypothesis that the large proportion of mutant neoantigens in mismatch repair-deficient cancers make them sensitive to immune checkpoint blockade, regardless of the cancers' tissue of origin.","journal":"Science","year":2017,"id":6826,"datarank":15.724348864625073,"base_score":8.787372988731876,"endowment":8.787372988731876,"self_citation_contribution":1.3181059483097817,"citation_network_contribution":14.406242916315291,"self_endowment_contribution":1.3181059483097817,"citer_contribution":14.406242916315291,"corpus_percentile":88.0,"corpus_rank":1987,"citation_count":6550,"citer_count":183,"citers_with_citation_signal":183,"citers_with_endowment":183,"datacite_reuse_total":0,"is_dataset":false,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2017-07-28","authors":[{"id":62879,"name":"Jennifer N. Durham","orcid":"0000-0001-9097-9125","position":1,"is_corresponding":false},{"id":62880,"name":"Kellie N. 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