Furthermore, the PA/PI‐ND nanocage induced an effective cell cycle arrest, enhanced TAM repolarization, inhibited Treg cell function, and improved penetration of CD4+ and CD8+ T cells into the tumor tissue and antitumor activity utilizing the novel triple‐interlocked combination therapy on chemotherapy, immunotherapy, and chemoimmunotherapy. The gene discussed is CD8A; the disease is neoplasm.