Dysfunction and stemness of tumor-infiltrating T cells are triggered by a common mechanism

The paradox of tumor immunology is that tumor infiltrating lymphocytes (TILs) are dysfunctional in situ and yet are capable of stem cell-like behavior with self-renewal, massive expansion, multipotency, and eradication of large metastatic tumors. Here we report that the overabundance of potassium in the tumor microenvironment (TME) can explain both phenomena. Overall design: Ctrl (or Samples labelled V- Vehicle) and elevated potassium (or Samples labelled K) were used to perfrom ChiP assays. CD8+ T cells from pmel mice were stimulated in vitro with 1 µM human gp100 peptide (10 µg/ml) in Ctrl (V) or elevated potassium (K) for 5 days and secondary re-stimulation was done for 48hrs with plate-bound anti-CD3 (1 µg/ml; BD Biosciences) and soluble anti-CD28 (1 µg/ml; BD Biosciences) and expanded in culture medium (Ctrl /K) containing 60 IU/mL of IL-2 for a total of 10 days.