CD4 and neoplasm: First, CD4+ T cells primed by the tumor cells may get activated, upregulate 4-1BB on their surface, and become the direct target of SA-4-1BBL following vaccination for i) licensing DCs through CD40-CD40L interaction, ii) generation of cytokines that help CD8+ T cells for expansion and effector differentiation, and iii) providing survival benefits by regulating extrinsic, such as TRAIL, and/or intrinsic, such as Bcl-xL, apoptotic mechanisms [38].