TNF and neoplasm: Fumarate released by tumors targets ZAP70—a key kinase in the T cell receptor (TCR) signaling pathway—via succinylation, its inactivation blocks TCR signal transduction, preventing CD8+ T cells from effective activation, proliferation, and secretion of effector factors (e.g., IFN-γ, TNF-α), thereby impairing their tumor-killing capacity (322).