Potassium shapes antitumor immunity

Can potassium provide a tool for better cancer immunotherapy? 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.