T cell stemness and dysfunction in tumors are triggered by a common mechanism
- Authors
- Vodnala, Suman Kumar; Eil, Robert; Kishton, Rigel J.; Sukumar, Madhusudhanan; Yamamoto, Tori N.; Ngoc-Han Ha; Lee, Ping-Hsien; Shin, MinHwa; Patel, Shashank J.; Yu, Zhiya; Palmer, Douglas C.; Kruhlak, Michael J.; Liu, Xiaojing; Locasale, Jason W.; Huang, Jing; Roychoudhuri, Rahul; Finkel, Toren; Klebanoff, Christopher A.; Restifo, Nicholas P.
- Issue Date
- Mar-2019
- Publisher
- American Association for the Advancement of Science
- Citation
- Science, v.363, no.6434, pp 1417 - +
- Indexed
- SCI
SCIE
SCOPUS
- Journal Title
- Science
- Volume
- 363
- Number
- 6434
- Start Page
- 1417
- End Page
- +
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/2258
- DOI
- 10.1126/science.aau0135
- ISSN
- 0036-8075
1095-9203
- Abstract
- A paradox of tumor immunology is that tumor-infiltrating lymphocytes are dysfunctional in situ, yet are capable of stem cell-like behavior including self-renewal, expansion, and multipotency, resulting in the eradication of large metastatic tumors. We find that the overabundance of potassium in the tumor microenvironment underlies this dichotomy, triggering suppression of T cell effector function while preserving stemness. High levels of extracellular potassium constrain T cell effector programs by limiting nutrient uptake, thereby inducing autophagy and reduction of histone acetylation at effector and exhaustion loci, which in turn produces CD8(+) T cells with improved in vivo persistence, multipotency, and tumor clearance. This mechanistic knowledge advances our understanding of T cell dysfunction and may lead to novel approaches that enable the development of enhanced T cell strategies for cancer immunotherapy.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - 4. Research institute > Research Institute of Molecular Medicine and Nutrition > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.