T cell stemness and dysfunction in tumors are triggered by a common mechanism Journal Article
| Authors: | Vodnala, S. K.; Eil, R.; Kishton, R. J.; Sukumar, M.; Yamamoto, T. N.; Ha, N. H.; Lee, P. H.; Shin, M.; Patel, S. J.; Yu, Z.; Palmer, D. C.; Kruhlak, M. J.; Liu, X.; Locasale, J. W.; Huang, J.; Roychoudhuri, R.; Finkel, T.; Klebanoff, C. A.; Restifo, N. P. |
| Article Title: | T cell stemness and dysfunction in tumors are triggered by a common mechanism |
| 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. 2017 © The Authors, some rights reserved. |
| Journal Title: | Science |
| Volume: | 363 |
| Issue: | 6434 |
| ISSN: | 0036-8075 |
| Publisher: | American Association for the Advancement of Science |
| Date Published: | 2019-03-29 |
| Start Page: | eaau0135 |
| Language: | English |
| DOI: | 10.1126/science.aau0135 |
| PUBMED: | 30923193 |
| PROVIDER: | scopus |
| PMCID: | PMC8194369 |
| DOI/URL: | |
| Notes: | Source: Scopus |
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