The observation that signaling via 4-1BB prevents antigen-, TGF-β, and tumor-mediated conversion of conventional CD4+ T cells into iTreg cells via IFN-γ is consistent with and provide a plausible mechanistic insight into our recently published studies demonstrating that vaccination with SA-4-1BBL and human papilloma virus E7 TAA showed robust therapeutic efficacy against established TC-1 tumors [12], [13], [35]. Here, CD4 is linked to neoplasm.