Science· 2017Q1
Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade
- 6,692citations
- Q1SCImago
- 2017year
Short summary
Solid tumors with mismatch repair deficiency show a high response rate to PD-1 blockade therapy, with 53% objective radiographic responses and 21% complete responses across 12 tumor types.
AI-generated from the title and abstract; the full text is not read.
Key points
- 53% of patients with mismatch repair-deficient solid tumors responded to PD-1 blockade.
- 21% of patients achieved complete radiographic responses.
- Responses were durable, with median progression-free and overall survival not yet reached.
- High mutation burden from mismatch repair deficiency generates neoantigens that prime T cell responses.
AI-generated from the title and abstract; the full text is not read.
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.
The authors' abstract, as published at the source. Science, 2017 · DOI ↗
Continue with a free account
Ask the paper: 3 free questions a day about this paper; save it, get its citation, new summaries every day for your field. Takeaways are Premium.
Continue free on the webSign in with Google or Apple; no card needed. You come back to this paper.
On your phone:
Field: Pathology and Forensic Medicine
Pathology and Forensic MedicineMedicine