Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Lung inflammatory injury and tissue repair (Jul 2023)
    • Immune Environment in Glioblastoma (Feb 2023)
    • Korsmeyer Award 25th Anniversary Collection (Jan 2023)
    • Aging (Jul 2022)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Research letters
    • Letters to the editor
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Research letters
  • Letters to the editor
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
Immune activation and response to pembrolizumab in POLE-mutant endometrial cancer
Janice M. Mehnert, … , Jonathan Cheng, Shridar Ganesan
Janice M. Mehnert, … , Jonathan Cheng, Shridar Ganesan
Published May 9, 2016
Citation Information: J Clin Invest. 2016;126(6):2334-2340. https://doi.org/10.1172/JCI84940.
View: Text | PDF
Brief Report Oncology

Immune activation and response to pembrolizumab in POLE-mutant endometrial cancer

  • Text
  • PDF
Abstract

Antibodies that target the immune checkpoint receptor programmed cell death protein 1 (PD-1) have resulted in prolonged and beneficial responses toward a variety of human cancers. However, anti–PD-1 therapy in some patients provides no benefit and/or results in adverse side effects. The factors that determine whether patients will be drug sensitive or resistant are not fully understood; therefore, genomic assessment of exceptional responders can provide important insight into patient response. Here, we identified a patient with endometrial cancer who had an exceptional response to the anti–PD-1 antibody pembrolizumab. Clinical grade targeted genomic profiling of a pretreatment tumor sample from this individual identified a mutation in DNA polymerase epsilon (POLE) that associated with an ultramutator phenotype. Analysis of The Cancer Genome Atlas (TCGA) revealed that the presence of POLE mutation associates with high mutational burden and elevated expression of several immune checkpoint genes. Together, these data suggest that cancers harboring POLE mutations are good candidates for immune checkpoint inhibitor therapy.

Authors

Janice M. Mehnert, Anshuman Panda, Hua Zhong, Kim Hirshfield, Sherri Damare, Katherine Lane, Levi Sokol, Mark N. Stein, Lorna Rodriguez-Rodriquez, Howard L. Kaufman, Siraj Ali, Jeffrey S. Ross, Dean C. Pavlick, Gyan Bhanot, Eileen P. White, Robert S. DiPaola, Ann Lovell, Jonathan Cheng, Shridar Ganesan

×

Figure 2

Comparison of immune markers in POLE, MSI, and MSS endometrial cancers in the TCGA data set.

Options: View larger image (or click on image) Download as PowerPoint
Comparison of immune markers in POLE, MSI, and MSS endometrial cancers i...
(A) The relative numbers of nonsynonymous mutations found in POLE-mutant, MSI, and MSS endometrial cancers. (B) Heat map showing relative expression of differentially expressed immune-related genes in POLE-mutant, MSI, and MSS endometrial cancers. Number of samples: 27 POLE, 64 MSI, 104 MSS. Box plots (shown in A) use the following default convention: the horizontal line represents the median value, the box covers the interquartile range (IQR), the whiskers cover values within 1.5 IQR beyond the box, and values beyond 1.5 IQR are represented as dots.

Copyright © 2023 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts