Epigenetic therapy activates type I interferon signaling in murine ovarian cancer to reduce immunosuppression and tumor burden
Abstract
Therapies that activate the host immune system have shown tremendous promise for a variety of solid tumors. However, in most cancer types, fewer than half of patients respond to these immunotherapies. We propose epigenetic therapy as a mechanism to sensitize tumors to immune checkpoint therapy. We have shown that inhibiting DNA methylation triggers a viral defense pathway in tumors. Here we show that epigenetic therapy in a mouse model of ovarian cancer increases the numbers of activated immune cells, and that this is dependent on the interferon antiviral response. The combination of epigenetic therapy and immune checkpoint blockade leads to the greatest reduction in tumor burden and increase in survival, and may hold the greatest promise for patients.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Dec 04, 2017
- Source ID
- 10.1073/pnas.1712514114
Entities
People
- Chien-fu Hung
- Cynthia A. Zahnow
- Dimitrios Mathios
- Glenn S. Cowley
- Huili Li
- Ie-Ming Shih
- Karla R. Wiehagen
- Katherine B. Chiappinelli
- Kurtis E. Bachman
- Lauren M. Murphy
- Meghan E. Travers
- Meredith L. Stone
- Michael J. Topper
- Michael Lim
- Pamela L. Strissel
- Reiner Strick
- Stephen B. Baylin
- Tian-li Wang
- Vipul Bhargava
Organizations
- Adelson Foundation
- Johnson & Johnson Pharmaceutical Research and Development
- National Institutes of Health
- Samuel Waxman Cancer Research Foundation
- United States Department of Defense