肿瘤坏死因子在肿瘤发生发展中的作用及其机制研究进展OA

Tumor necrosis factor(TNF)plays a central dual role in oncology:it not only drives potent antitumor immunity but also serves as a key factor promoting malignant tumor progression and metastasis.This functional differentiation is rooted in the dynamic regulation of the tumor necrosis factor receptor 1/2(TNFR1/2)signaling pathways.The elaborate assembly of intracellular signalosomes and critical post-trans-lational modifications such as the palmitoylation of Receptor-Interacting Serine/Threonine-Protein Kinase 1(RIPK1)and others collectively determine the cellular fate choice between apoptosis and survival.Within the tumor microenvironment,TNF reshapes the immune landscape in a highly context-dependent manner,by ei-ther enhancing the metabolic fitness of natural killer cells or inducing immunosuppressive regulatory T cell subsets.To address the toxicity dilemma of systemic TNF administration,the current research paradigm has shifted towards spatiotemporal control.Strategies exemplified by the oncolytic virus TILT-123,which enables precise localized intratumoral production of TNF-α and Interleukin-2,have demonstrated potent antitumor ef-ficacy and the potential to induce systemic antitumor immune memory in clinical trials.Future research will focus on developing multispecific molecules,intelligent drug delivery systems,and systematically deciphering the functional network of the entire TNF superfamily,aiming to usher in a new era of more precise tumor im-munological intervention.