The number of CD8+ T cells in pancreatic cancer TME is significantly reduced when IL-35-producing regulatory T cells and B cells aggregate, due to IL-35-promoted activation of STAT3 inhibiting the intratumoral infiltration and effector functions of CD8+ T cells by suppressing CXCR3, CCR5, and IFN-γ expression [45]. Here, CD8A is linked to familial pancreatic carcinoma.