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

“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.

- Authors: Dung Thi Le, Jennifer N. Durham, Kellie Nicole Smith, Hao Wang, Bjarne R. Bartlett, Laveet K. Aulakh, Steve Lu, Holly Kemberling, Cara Wilt, Brandon S. Luber et al.
- Published: July 27, 2017
- Field: Medicine
- DOI: https://doi.org/10.1126/science.aan6733
- Source: https://www.ncbi.nlm.nih.gov/pmc/articles/5576142

## 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.

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