Interestingly, several studies have demonstrated that in both chronic viral disease and in established tumours (i.e., settings where T cells can become functionally ‘exhausted’) the antigen-specific cells that undergo a profound proliferative burst following a-PD-1 administration exhibit a defined PD-1+ TCF-1+ phenotype, demarcating them as “precursor-exhausted” T cells [165,167] (TPEX), while more terminally differentiated and fully exhausted PD-1HI Tim-3+ TCF-1− cells do not exert clinically relevant anti-tumour function [168,169,170,171,172]. This evidence concerns the gene HAVCR2 and viral load.