CX3CL1 release is associated with enhanced immunogenicity of dying cancer cells.

Immunogenic cell death (ICD) stands as a burgeoning paradigm within the realm of cancer immunotherapy. The pivotal determinants governing ICD encompass antigenicity, denoting the presence of antigens, and adjuvanticity, signifying the release of damage-associated molecular patterns (DAMPs) and cytokines/chemokines. CX3CL1, also recognized as neurotactin or fractalkine, is a chemokine intricately intertwined in the landscape of cellular signaling and immunology, contributing to the tolerogenic properties of apoptosis.

The primary objective of this study was to scrutinize the involvement of CX3CL1 in the context of immunogenic apoptosis induced by mitoxantrone (MTX) in cancer cells.

Our findings underscore the substantial role played by CX3CL1 release in eliciting an immunogenic response towards different types of MTX-treated cancer cells, with enhanced CX3CL1 release observed solely in MTX-treated cancer cells. Furthermore, the addition of recombinant CX3CL1 to non-immunogenic doses of MTX-treated cancer cells in a mice prophylactic tumor vaccination model resulted in a reversal to an immunogenic response, effectively impeding tumor formation. Moreover, analysis of melanoma patient data (TCGA SKCM dataset, 93 patients) revealed enhanced survival rates in individuals exhibiting elevated levels of T-cells expressing the receptor for CX3CL1. These data collectively suggest that CX3CL1 may serve as a principal mediator in conferring immunogenicity to cell death.