CD8A and neoplasm: Two primary mechanisms of 4-1BB-driven suppression have been suggested, either promoting the accumulation and activity of conventional CD4+Foxp3+ Treg that can express 4-1BB, or more in-line with the tumor and virus literature on 4-1BB, inducing the differentiation or reactivation of CD8 T cells, either into CTL or a type of CD8+ Treg that makes IFN-γ and can suppress the normal inflammatory response of CD4 T cells or B cells (16, 22, 140, 141, 143, 144, 151–154).