Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising/recruitment
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All...
  • Videos
  • Collections
    • Recently published
    • Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • About
  • Editors
  • Consulting Editors
  • For authors
  • Transfers
  • Current issue
  • Past issues
  • By specialty
  • Contact
  • Recently published
  • Technical Advances
  • Clinical Medicine
  • Editorials
  • Top read articles
Synergy of radiotherapy and PD-1 blockade in Kras-mutant lung cancer
Grit S. Herter-Sprie, … , Alec C. Kimmelman, Kwok-Kin Wong
Grit S. Herter-Sprie, … , Alec C. Kimmelman, Kwok-Kin Wong
Published June 16, 2016
Citation Information: JCI Insight. 2016;1(9):e87415. https://doi.org/10.1172/jci.insight.87415.
View: Text | PDF
Categories: Research Article Immunology Oncology

Synergy of radiotherapy and PD-1 blockade in Kras-mutant lung cancer

  • Text
  • PDF
Abstract

Radiation therapy (RT), a critical modality in the treatment of lung cancer, induces direct tumor cell death and augments tumor-specific immunity. However, despite initial tumor control, most patients suffer from locoregional relapse and/or metastatic disease following RT. The use of immunotherapy in non–small-cell lung cancer (NSCLC) could potentially change this outcome by enhancing the effects of RT. Here, we report significant (up to 70% volume reduction of the target lesion) and durable (up to 12 weeks) tumor regressions in conditional Kras-driven genetically engineered mouse models (GEMMs) of NSCLC treated with radiotherapy and a programmed cell death 1 antibody (αPD-1). However, while αPD-1 therapy was beneficial when combined with RT in radiation-naive tumors, αPD-1 therapy had no antineoplastic efficacy in RT-relapsed tumors and further induced T cell inhibitory markers in this setting. Furthermore, there was differential efficacy of αPD-1 plus RT among Kras-driven GEMMs, with additional loss of the tumor suppressor serine/threonine kinase 11/liver kinase B1 (Stk11/Lkb1) resulting in no synergistic efficacy. Taken together, our data provide evidence for a close interaction among RT, T cells, and the PD-1/PD-L1 axis and underscore the rationale for clinical combinatorial therapy with immune modulators and radiotherapy.

Authors

Grit S. Herter-Sprie, Shohei Koyama, Houari Korideck, Josephine Hai, Jiehui Deng, Yvonne Y. Li, Kevin A. Buczkowski, Aaron K. Grant, Soumya Ullas, Kevin Rhee, Jillian D. Cavanaugh, Neermala Poudel Neupane, Camilla L. Christensen, Jan M. Herter, G. Mike Makrigiorgos, F. Stephen Hodi, Gordon J. Freeman, Glenn Dranoff, Peter S. Hammerman, Alec C. Kimmelman, Kwok-Kin Wong

×

Full Text PDF | Download (1.71 MB)

Follow JCI Insight:
Copyright © 2019 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts