Potassium shapes antitumor immunity

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Science  29 Mar 2019:
Vol. 363, Issue 6434, pp. 1395-1396
DOI: 10.1126/science.aaw8800

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T cells protect us from infections and tumors. Nonetheless, cancers grow, persist, and metastasize, even in the presence of tumor-infiltrating lymphocytes (TILs), which include T cells with tumor cell–killing capabilities. This lack of immune control stems from the functional exhaustion, or hyporesponsiveness, of TILs as a consequence of chronic antigen exposure, poor expression of rejection antigens by tumor cells, hypoxia, lack of nutrients or substrates, and/or other suppressive mechanisms in the tumor microenvironment (TME). Despite these challenges, tumor antigen–specific TILs with stem cell–like behavior can mediate tumor destruction after successful immunotherapy, such as immune checkpoint blockade (1). Finding mechanisms that maintain the stemness of TILs may lead to improved cancer immunotherapies. On page 1417 of this issue, Vodnala et al. (2) identify the concentration of extracellular potassium in the TME as a determinant of the dysfunction and stemness of CD8+ TILs. This helps explain how tumors progress in the presence of T cells that could clear them and suggests new approaches to boost T cell stemness in cancer immunotherapy.