TNF
TNF (tumor necrosis factor) is the master cytokine of acute inflammation: a signaling protein that coordinates the systemic response to infection and, depending on context, kills tumor cells directly or drives the inflammation that feeds them.
Function
TNF is produced mainly by activated macrophages as a membrane-bound protein cleaved to its soluble form. It signals through two receptors: TNFR1, present on nearly all cells, which recruits the TRADD complex and can launch either NF-κB survival transcription or caspase-8-mediated apoptosis (with necroptosis as a third outcome when caspases are blocked); and TNFR2, restricted to immune cells. Systemically, TNF induces fever, the acute-phase response, and endothelial activation — the physiology of sepsis is largely TNF physiology, which is why TNF blockade in sepsis trials failed.
In cancer
The name records the original observation: TNF kills tumors, and the factor was identified by its ability to necrose sarcoma transplants. The killing is real but narrow — many tumors resist TNF-induced apoptosis through NF-κB activation, and chronic TNF production in the tumor microenvironment promotes inflammation-driven carcinogenesis and metastasis. Anti-TNF antibodies (infliximab, adalimumab) transformed autoimmune therapy; in oncology, TNF is used only in isolated-limb perfusion for sarcoma.
Notes
- Human gene symbol: TNF (TNF-α); UniProt P01375; 233 amino acids (precursor); TNF cytokine family.