Journal
CELL
Volume 171, Issue 6, Pages 1284-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2017.10.022
Keywords
-
Categories
Funding
- Hodson Trust
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
- Commonwealth Foundation
- Stand Up To Cancer Jim Toth Sr. Breakthrough Prize in Lung Cancer
- SWCRF Collaboration for a Cure
- Defense Health Program (DOD0), through the Department of Defense Ovarian Cancer Research Program, Teal Innovator Award [OC130454/W81XWH-14-1-0385]
- National Cancer Institute [CA121113, CA006973, CA180950]
- Van Andel Research Institute through the Van Andel Research Institute - Stand Up To Cancer Epigenetics Dream Team
Ask authors/readers for more resources
Combining DNA-demethylating agents (DNA methyltransferase inhibitors [DNMTis]) with histone deacetylase inhibitors (HDACis) holds promise for enhancing cancer immune therapy. Herein, pharmacologic and isoform specificity of HDACis are investigated to guide their addition to a DNMTi, thus devising a new, low-dose, sequential regimen that imparts a robust anti-tumor effect for non-small-cell lung cancer (NSCLC). Using in-vitro-treated NSCLC cell lines, we elucidate an interferon alpha/beta-based transcriptional program with accompanying upregulation of antigen presentation machinery, mediated in part through double-stranded RNA (dsRNA) induction. This is accompanied by suppression of MYC signaling and an increase in the T cell chemoattractant CCL5. Use of this combination treatment schema in mouse models of NSCLC reverses tumor immune evasion and modulates T cell exhaustion state towards memory and effector T cell phenotypes. Key correlative science metrics emerge for an upcoming clinical trial, testing enhancement of immune checkpoint therapy for NSCLC.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available