TNF and familial pancreatic carcinoma: Elevated GDF-15 promotes NF-kB activation, inhibits macrophage activity, and blocks the synthesis of tumor necrosis factor TNF-α and NO through inhibition of TGF-β-activated kinase1 (TAK1), which leads to the immune escape of tumor cells.[30] Fibroblasts in the tumor microenvironment play a crucial role in the development of pancreatic cancer.