DNA methyltransferase inhibition upregulates MHC-I to potentiate cytotoxic T lymphocyte responses in breast cancer

Na Luo, Mellissa J. Nixon, Paula I. Gonzalez-Ericsson, Violeta Sanchez, Susan R. Opalenik, Huili Li, Cynthia A. Zahnow, Michael L. Nickels, Fei Liu, Mohammed N. Tantawy, Melinda E. Sanders, H. Charles Manning and Justin M. Balko ()
Additional contact information
Na Luo: Nankai University
Mellissa J. Nixon: Vanderbilt University Medical Center
Paula I. Gonzalez-Ericsson: Vanderbilt University Medical Center
Violeta Sanchez: Vanderbilt University Medical Center
Susan R. Opalenik: Vanderbilt University Medical Center
Huili Li: Penn State Health Milton S. Hershey Medical Center
Cynthia A. Zahnow: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Michael L. Nickels: Vanderbilt University Medical Center
Fei Liu: Vanderbilt University Medical Center
Mohammed N. Tantawy: Vanderbilt University Medical Center
Melinda E. Sanders: Vanderbilt University Medical Center
H. Charles Manning: Vanderbilt University Medical Center
Justin M. Balko: Vanderbilt University Medical Center

Nature Communications, 2018, vol. 9, issue 1, 1-11

Abstract: Abstract Potentiating anti-tumor immunity by inducing tumor inflammation and T cell-mediated responses are a promising area of cancer therapy. Immunomodulatory agents that promote these effects function via a wide variety of mechanisms, including upregulation of antigen presentation pathways. Here, we show that major histocompatibility class-I (MHC-I) genes are methylated in human breast cancers, suppressing their expression. Treatment of breast cancer cell lines with a next-generation hypomethylating agent, guadecitabine, upregulates MHC-I expression in response to interferon-γ. In murine tumor models of breast cancer, guadecitabine upregulates MHC-I in tumor cells promoting recruitment of CD8+ T cells to the microenvironment. Finally, we show that MHC-I genes are upregulated in breast cancer patients treated with hypomethylating agents. Thus, the immunomodulatory effects of hypomethylating agents likely involve upregulation of class-I antigen presentation to potentiate CD8+ T cell responses. These strategies may be useful to potentiate anti-tumor immunity and responses to checkpoint inhibition in immune-refractory breast cancers.

Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-017-02630-w 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:9:y:2018:i:1:d:10.1038_s41467-017-02630-w

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

DOI: 10.1038/s41467-017-02630-w

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 ().