Moreover, co-expression of sPD-L2 with other soluble mediators such as PD-L1, CD137, TIM-3 BTLA-4 and CEA has been associated with favorable clinical response indicating a synergistic effect of these soluble mediators with each other to induce modulatory effects within the tumor microenvironment (18, 72). This evidence concerns the gene TNFRSF9 and neoplasm.