HSP90 inhibition enhances cancer immunotherapy by upregulating interferon response genes

Rina M. Mbofung, Jodi A. McKenzie, Shruti Malu, Min Zhang, Weiyi Peng, Chengwen Liu, Isere Kuiatse, Trang Tieu, Leila Williams, Seram Devi, Emily Ashkin, Chunyu Xu, Lu Huang, Minying Zhang, Amjad H. Talukder, Satyendra C. Tripathi, Hiep Khong, Nikunj Satani, Florian L. Muller, Jason Roszik, Timothy Heffernan, James P. Allison, Gregory Lizee, Sam M. Hanash, David Proia, Rodabe Amaria, R. Eric Davis and Patrick Hwu ()
Additional contact information
Rina M. Mbofung: The University of Texas MD Anderson Cancer Center
Jodi A. McKenzie: The University of Texas MD Anderson Cancer Center
Shruti Malu: The University of Texas MD Anderson Cancer Center
Min Zhang: The University of Texas MD Anderson Cancer Center
Weiyi Peng: The University of Texas MD Anderson Cancer Center
Chengwen Liu: The University of Texas MD Anderson Cancer Center
Isere Kuiatse: The University of Texas MD Anderson Cancer Center
Trang Tieu: The University of Texas MD Anderson Cancer Center
Leila Williams: The University of Texas MD Anderson Cancer Center
Seram Devi: The University of Texas MD Anderson Cancer Center
Emily Ashkin: The University of Texas MD Anderson Cancer Center
Chunyu Xu: The University of Texas MD Anderson Cancer Center
Lu Huang: The University of Texas MD Anderson Cancer Center
Minying Zhang: The University of Texas MD Anderson Cancer Center
Amjad H. Talukder: The University of Texas MD Anderson Cancer Center
Satyendra C. Tripathi: The University of Texas MD Anderson Cancer Center
Hiep Khong: The University of Texas MD Anderson Cancer Center
Nikunj Satani: The University of Texas MD Anderson Cancer Center
Florian L. Muller: The University of Texas MD Anderson Cancer Center
Jason Roszik: The University of Texas MD Anderson Cancer Center
Timothy Heffernan: The University of Texas MD Anderson Cancer Center
James P. Allison: The University of Texas MD Anderson Cancer Center
Gregory Lizee: The University of Texas MD Anderson Cancer Center
Sam M. Hanash: The University of Texas MD Anderson Cancer Center
David Proia: Synta Pharmaceuticals Inc.
Rodabe Amaria: The University of Texas MD Anderson Cancer Center
R. Eric Davis: The University of Texas MD Anderson Cancer Center
Patrick Hwu: The University of Texas MD Anderson Cancer Center

Nature Communications, 2017, vol. 8, issue 1, 1-8

Abstract: Abstract T-cell-based immunotherapies are promising treatments for cancer patients. Although durable responses can be achieved in some patients, many patients fail to respond to these therapies, underscoring the need for improvement with combination therapies. From a screen of 850 bioactive compounds, we identify HSP90 inhibitors as candidates for combination with immunotherapy. We show that inhibition of HSP90 with ganetespib enhances T-cell-mediated killing of patient-derived human melanoma cells by their autologous T cells in vitro and potentiates responses to anti-CTLA4 and anti-PD1 therapy in vivo. Mechanistic studies reveal that HSP90 inhibition results in upregulation of interferon response genes, which are essential for the enhanced killing of ganetespib treated melanoma cells by T cells. Taken together, these findings provide evidence that HSP90 inhibition can potentiate T-cell-mediated anti-tumor immune responses, and rationale to explore the combination of immunotherapy and HSP90 inhibitors.

Date: 2017
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-017-00449-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00449-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-017-00449-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().