“Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade” (2017), by Dung Thi Le et al. Medicine research paper. Original abstract below, unchanged. No free PDF was found.

Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade

Dung Thi Le, Jennifer N. Durham, Kellie Nicole Smith et al. · July 27, 2017 · Medicine

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.

Source page DOI: 10.1126/science.aan6733