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

2020-05-01T19:26:33Z (GMT) by Dung Le
Dataset supporting publication: Le, D. T., Durham, J. N., Smith, K. N., Wang, H., Bartlett, B. R., Aulakh, L. K., ... & Wong, F. (2017). Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science, 357(6349), 409-413.

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.

Supplemental Tables included here: Baseline characteristics, response to treatment, and somatic mutations of subjects enrolled in the trial. The data cutoff was 19 December 2016.