Identifying a Novel Role for Fractalkine (CX3CL1) in Memory CD8 + T Cell Accumulation in the Omentum of Obesity-Associated Cancer Patients

Early human evidence such as case series or small samples is exploring possible benefits.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

The omentum is enriched with pro-inflammatory effector memory CD8 + T cells in patients with the obesity-associated malignancy, esophagogastric adenocarcinoma (EAC) and we have identified the chemokine macrophage inflammatory protein-1alpha as a key player in their active migration to this inflamed tissue. More recently, others have established that subsets of memory CD8 + T cells can be classified based on their surface expression of CX3CR1; the specific receptor for the inflammatory chemokine fractalkine. CD8 + T cells expressing intermediate levels (CX3CR1 INT ) are defined as peripheral memory, those expressing the highest levels (CX3CR1 HI ) are effector memory/terminally differentiated and those lacking CX3CR1 (CX3CR1 NEG ) are classified as central memory. To date, the fractalkine:CX3CR1 axis has not been examined in the context of CD8 + T cell enrichment in the omentum and here we examine this chemokines involvement in the accumulation of memory CD8 + T cells in the omentum of EAC patients. Our data show that fractalkine is significantly enriched in the omentum of EAC patients and drives migration of T cells derived from EAC patient blood. Furthermore, CX3CR1 is endocytosed specifically by CD8 + T cells upon encountering fractalkine, which is consistent with the significantly diminished frequencies of CX3CR1 INT and CX3CR1 HI CD8 + T cells in the fractalkine-rich enviro

Evidence level

Early human evidence such as case series or small samples is exploring possible benefits.

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