Potent small‐molecule inhibitors of Arf1, designated as DU101 and DU102, have been discovered to initiate a series of aging processes in CSCs and systemically remodeled immune microenvironment including increasing the population of tumor‐associated CD8+ CD4+ double‐positive T (DPT) cells in preclinical mouse cancer and PDX models. Here, ARF1 is linked to cancer.