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

dataset
posted on 01.05.2020 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.

Funding

Swim Across America Laboratory at Johns Hopkins

Ludwig Center for Cancer Genetics and Therapeutics

Howard Hughes Medical Institutes

Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins

2017 Stand Up to Cancer Colon Cancer Dream Team

Commonwealth Fund

Banyan Gate Foundation

Lustgarten Foundation for Pancreatic Cancer Research

Bloomberg Foundation

Sol Goldman Pancreatic Cancer Research Center

Merck & Co. Inc.

SPORE in Gastrointestinal Cancers

National Cancer Institute

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Regional Oncology Research Center

National Cancer Institute

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Cyclophosphamide modified GM-CSF pancreatic tumor vaccine + listeria-mesothelin

National Cancer Institute

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Molecular Genetic Analysis of Colorectal Cancer

National Cancer Institute

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Correlates of antitumor immunity in colorectal cancers and anti PD1 therapy

National Cancer Institute

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INCIDENCE AND MOLECULAR SCREENING FOR HEREDITARY CANCER

National Cancer Institute

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Cancer Center Support Grant

National Cancer Institute

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GENES FROM THE FAP LOCUS

National Cancer Institute

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History

Select an IC:

  • CA - National Cancer Institute (NCI)

Is this associated with a publication?

Yes

DOI(s) of associated publication(s):

I confirm there is no human identifiable information in this dataset.

Yes

Licence

Exports