CD4 and neoplasm: Although 4-1BB costimulation transduces a robust costimulatory signal, mainly acting on CD8+ T cells (Habib-Agahi et al., 2007), mice that constitutively express 4-1BB on CD4+ T cells exhibited heightened and sustained proliferative activity and enhancement of T-cell priming, driving TH1 immune responses, increasing the number of tumor-infiltrating lymphocytes (TILs) in tumor masses, augmenting IFN-γ production by T-cell population, mediating tumor suppression, and prolonging mice survival (Kim et al., 2003).