In the present study, by activating tumor-reactive CD4+ T cells in vitro, we demonstrated that tumor-specific CD4+ T cells could delay metastatic foci formation, informing a potential strategy for future clinical treatment, particularly for patients who develop metastatic disease and for the patients who are resistance to CD8+ T cells because of the MHC class I loss (41, 42). This evidence concerns the gene CD8A and metastatic neoplasm.