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The reported role of CX3CL1 as a key regulator of cytotoxic T cell-mediated immunity is supported by several studies that demonstrate CX3CL1 as an important TIL-recruiting chemokine and a positive prognostic factor in colorectal, breast, and lung cancer. Such reports are conflicting with an overwhelming number of studies demonstrating a pro-tumorigenic and pro-metastatic role of CX3CL1 across multiple blood and solid malignancies.This chapter will review the unique structure, function, and biology of CX3CL1 and address the diversity of i