CX3CL1: a key switch of cell death immunogenicity.

CX3CL1 (fractalkine) is a unique chemokine with dual roles in cancer biology, capable of exerting both tumor-promoting and tumor-suppressive effects. Acting through its receptor CX3CR1, CX3CL1 facilitates immune evasion, angiogenesis, metastasis, and tumor cell survival and proliferation by recruiting immunosuppressive myeloid-derived suppressor cells. Conversely, it can enhance antitumor immunity by attracting cytotoxic T lymphocytes, natural killer cells, and dendritic cells into the tumor microenvironment. CX3CL1 has also been implicated in promoting immunogenic cell death-induced anticancer immune responses. However, excessive expression of CX3CL1 may paradoxically suppress immune activation, highlighting the importance of dose and context in its application. CX3CL1-based gene or mRNA therapies, particularly in combination with immune checkpoint inhibitors, show promising potential for cancer treatment.