Abstract Inhibiting myeloid-derived suppressor cells (MDSC) might be the ultimate barrier to break down tumor defenses and recover the preexisting T-cell immunity required to respond to immunotherapy. However, selectively intercepting MDSCs to prove their etiologic role in cancer progression is not an easy task. In this issue of Cancer Research, Yin and colleagues demonstrate unequivocally that the Aurora A kinase inhibitor, alisertib, specifically neutralizes MDSCs and triggers the rapid accrual of cytotoxic T cells, with consequent tumor clearance potentiated by PD-L1 blockade. Translating this approach into the clinic might rescue tumor immunity in immune-desert landscapes. See related article by Yin et al., p. 3431