CX3CL1 switch of cell death immunogenicity
CX3CL1 plays a dual role in cancer: promoting tumor growth via angiogenesis, metastasis, and immune suppression yet also enhancing antitumor immunity by recruiting CD8+ T cells, natural killer cells, and dendritic cells.
Its pro- or antitumor effects are dose and context-dependent, with low levels boosting immunogenic cell death and high levels potentially triggering immune tolerance.
CX3CL1 is regulated by p53 and influences apoptosis, antigen presentation, and the balance between immunogenic and tolerogenic responses.
Therapeutically, modulating CX3CL1 levels or targeting the CX3CL1/ CX3CR1 axis shows promise in cancer immunotherapy but must be carefully controlled to avoid unwanted side effects.
Emerging strategies include CX3CR1+ chimeric antigen receptor T cell delivery and combinatorial therapies to optimize its immune-stimulating properties while limiting tumor-promoting outcomes.
https://www.cell.com/trends/cancer/fulltext/S2405-8033(25)00206-7
