L-ASNase was originally developed to exploit the asparagine auxotrophy of acute lymphoblastic leukemia, recent mechanistic and translational studies demonstrate that transient asparagine depletion remodels the tumor microenvironment (TME) in ways that can potentiate CD8+ T-cell responses and increase sensitivity to PD-1/PD-L1 blockade (155). The gene discussed is CD8A; the disease is neoplasm.