Epigenetic modulation of immune synaptic-cytoskeletal networks potentiates γδ T cell-mediated cytotoxicity in lung cancer

Rueyhung R. Weng, Hsuan-Hsuan Lu, Chien-Ting Lin, Chia-Chi Fan, Rong-Shan Lin, Tai-Chung Huang, Shu-Yung Lin, Yi-Jhen Huang, Yi-Hsiu Juan, Yi-Chieh Wu, Zheng-Ci Hung, Chi Liu, Xuan-Hui Lin, Wan-Chen Hsieh, Tzu-Yuan Chiu, Jung-Chi Liao, Yen-Ling Chiu, Shih-Yu Chen, Chong-Jen Yu and Hsing-Chen Tsai ()
Additional contact information
Rueyhung R. Weng: National Taiwan University Hospital
Hsuan-Hsuan Lu: National Taiwan University Hospital
Chien-Ting Lin: National Taiwan University
Chia-Chi Fan: National Taiwan University
Rong-Shan Lin: National Taiwan University
Tai-Chung Huang: National Taiwan University Hospital
Shu-Yung Lin: National Taiwan University Hospital
Yi-Jhen Huang: National Taiwan University
Yi-Hsiu Juan: National Taiwan University Hospital
Yi-Chieh Wu: National Taiwan University
Zheng-Ci Hung: National Taiwan University Hospital
Chi Liu: National Taiwan University
Xuan-Hui Lin: National Taiwan University
Wan-Chen Hsieh: Academia Sinica
Tzu-Yuan Chiu: Academia Sinica
Jung-Chi Liao: Academia Sinica
Yen-Ling Chiu: Yuan Ze University
Shih-Yu Chen: Academia Sinica
Chong-Jen Yu: National Taiwan University Hospital
Hsing-Chen Tsai: National Taiwan University Hospital

Nature Communications, 2021, vol. 12, issue 1, 1-18

Abstract: Abstract γδ T cells are a distinct subgroup of T cells that bridge the innate and adaptive immune system and can attack cancer cells in an MHC-unrestricted manner. Trials of adoptive γδ T cell transfer in solid tumors have had limited success. Here, we show that DNA methyltransferase inhibitors (DNMTis) upregulate surface molecules on cancer cells related to γδ T cell activation using quantitative surface proteomics. DNMTi treatment of human lung cancer potentiates tumor lysis by ex vivo-expanded Vδ1-enriched γδ T cells. Mechanistically, DNMTi enhances immune synapse formation and mediates cytoskeletal reorganization via coordinated alterations of DNA methylation and chromatin accessibility. Genetic depletion of adhesion molecules or pharmacological inhibition of actin polymerization abolishes the potentiating effect of DNMTi. Clinically, the DNMTi-associated cytoskeleton signature stratifies lung cancer patients prognostically. These results support a combinatorial strategy of DNMTis and γδ T cell-based immunotherapy in lung cancer management.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-22433-4 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:12:y:2021:i:1:d:10.1038_s41467-021-22433-4

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

DOI: 10.1038/s41467-021-22433-4

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 ().