PD-1/PD-L1 checkpoint inhibition therapy partially suppresses the appearance of exhausted T cells in patients with chronic infections and cancer, but it has also been shown that the development of exhausted CD8+ T cells during chronic LCMV infection could not be reverted, even by PD-1/PD-L1 checkpoint inhibition, when the production of IL-21 by CD4+ T cells was inadequate [42]. This evidence concerns the gene CD274 and cancer.