T cell stemness and dysfunction in tumors are triggered by a common mechanism

Suman K. Vodnala1,2, Robert Eil1,3,2, Rigel J. Kishton1,2, Madhusudhanan Sukumar1,2, Tori N. Yamamoto1,4,2, Ngoc-Han Ha5, Ping‐Hsien Lee1,2, MinHwa Shin5, Shashank Patel1,2, Zhiya Yu1,2, Douglas C. Palmer1,2, Michael J. Kruhlak6, Xiaojing Liu7, Jason W. Locasale7, Jing Huang5, Rahul Roychoudhuri8, Toren Finkel9, Christopher A. Klebanoff10,11,12, Nicholas P. Restifo1,2
1Center for Cell-Based Therapy, National Cancer Institute, Bethesda, MD 20892, USA.
2Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
3Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, 10065 USA
4Immunology Graduate Group, University of Pennsylvania, Philadelphia, PA 19104, USA
5Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA
6Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892 USA
7Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Duke University, Durham, NC 27710, USA
8Babraham Institute, Babraham Research Campus, Cambridge, UK
9Aging Institute, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
10Center for Cell Engineering and Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
11Parker Institute for Cancer Immunotherapy, New York, NY 10065, USA
12Weill Cornell Medical College Cornell University, New York, NY 10065, USA

Tóm tắt

Stemness against adversity T lymphocytes are powerful immune cells that can destroy tumors, but cancers have developed tricks to evade killing. Vodnala et al. found that potassium ions in the tumor microenvironment serve a dual role of influencing T cell effector function and stemness (see the Perspective by Baixauli Celda et al. ). Increased potassium impairs T cell metabolism and nutrient uptake, resulting in a starvation state known as autophagy. The increased potassium can also preserve T cells in a stem-like state where they retain the capacity to divide. These seemingly divergent processes are linked to the cellular distribution of acetyl–coenzyme A, which, when manipulated, can restore the ability of human T cells to eliminate tumors in mice. Science , this issue p. eaau0135 ; see also p. 1395

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