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Increased Expression of Fractalkine is Correlated with a Better Prognosis and an Increased Number of Both CD8⁺ T Cells and Natural Killer Cells in Gastric Adenocarcinoma

¹ Department of Digestive and General Surgery, Faculty of Medicine, Shimane University, Enyacho 89/1, Izumo, Japan
² Pathology Laboratory, Shimane University Hospital, Izumo, Japan

Correspondence: Address correspondence and reprint requests to: Miki Hyakudomi, MD; E-mail: nami46{at}med.shimane-u.ac.jp

Background: Fractalkine (CX3CL1) is the only CX3C chemokine that can chemoattract natural killer (NK) cells, CD8⁺ T cells, monocytes, and dendritic cells. Although experimental studies have demonstrated that Fractalkine expression by tumor cells is related to the infiltrating lymphocytes and initiates antitumor immunity, the clinical significance of Fractalkine remains to be elucidated in gastric adenocarcinoma.

Methods: Tissue sections from 158 patients with curatively resected T2 or T3 gastric adenocarcinoma were immunohistochemically stained for Fractalkine. Furthermore, to evaluate CD8⁺ T cells and NK cells infiltration, antibodies to CD8 and CD57 protein were respectively used for immunohistochemistry.

Results: A significant direct correlation was observed between the Fractalkine scores and the number of CD8⁺ T cells and NK cells using the Spearman rank correlation coefficient test (P = .0080, .0031, respectively). Furthermore, the high Fractalkine expression group (n = 67) showed a significantly better prognosis than the low Fractalkine expression group (n = 91) regarding the disease-free survival (P = .0016). In a multivariate analysis, the Fractalkine expression was identified as one of the independent prognosticators for disease-free survival (risk ratio, 2.5; P = .0147).

Conclusions: These data suggest that the expression of Fractalkine by tumor cells enhances the recruitment of CD8⁺ T cells and NK cells and induces both innate and adaptive immunity, thereby yielding a better prognosis in gastric adenocarcinoma. Fractalkine is a new independent predictor of the prognosis and can be a novel candidate for development of a more effective therapeutic strategy for gastric adenocarcinomas.

Key Words: Fractalkine • Gastric adenocarcinoma • CD8⁺ T cells • Natural killer cells • Prognostic factor

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