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

Suman Kumar Vodnala, Robert L Eil, Rigel J. Kishton, Madhusudhanan Sukumar, Tori N. Yamamoto, Ngoc‐Han Ha, Ping‐Hsien Lee, Min Hwa Shin, Shashank J. Patel, Zhiya Yu, Douglas C. Palmer, Michael J. Kruhlak, Xiaojing Liu, Jason W. Locasale, Jing Li Huang, Rahul Roychoudhuri, Toren Finkel, Christopher Austin Klebanoff, Nicholas P. Restifo

📄 Abstract

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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