The high expression of Fractalkine results in a better prognosis for colorectal cancer patients.
Local and systemic immune responses are impaired in patients with colorectal cancer (CRC) and it is known that the number of tumor infiltrating lymphocytes (TILs) is considerably few. On the other hand, some CRC cases in which many TIL were observed, survived longer than those cases with a small number of TIL. Considerable attention has been recently paid to the relationship between chemokines and tumor cells. Some chemokines recruit lymphocytes for tumor lesions. We made a hypothesis that Fractalkine, a CX3C chemokine, would recruit lymphocytes in the CRC and play an important role in anti-tumor immunity. We analyzed the expression level of Fractalkine in CRC cell lines as well as in clinical samples (n=80). The expression level of Fractalkine was thus found to correlate with the density of TIL (p<0.05). The CRC cases with a strong Fractalkine expression (n=50) showed a significantly better prognosis than those with a weak expression (n=30) (p<0.05). In addition, the Fractalkine expression was found to be an independent prognostic factor (p<0.05). We furthermore clarified that some of the tumor-infiltrating cells were natural killer cells and cytotoxic T cells expressed Fractalkine receptor. These data suggest that Fractalkine expressed in the tumor appears to recruit cytotoxic T cells and NK cells to the tumor site and these cytotoxic cells result in a better prognosis mediated by tumor cell cytotoxicity using a perforin and granzyme B mechanism. The expression level of Fractalkine was an essential biomarker for predicting the prognosis of patients with CRC. Fractalkine is considered to be one of the biomarkers for detecting patients with a high risk for recurrence, and who might therefore benefit from additional therapeutic strategies such as adjuvant therapy.
Ohta
Mitsuhiko
M
Division of Molecular and Surgical Oncology, Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Tsurumibaru, Beppu 874-0838, Japan.
Tanaka
Fumiaki
F
Yamaguchi
Hiroshi
H
Sadanaga
Noriaki
N
Inoue
Hiroshi
H
Mori
Masaki
M
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000737:chemistry; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000276:immunology / Q000401:mortality; D003593:Cytoplasm / Q000737:chemistry; D005260:Female; D015870:Gene Expression; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D055502:Secondary Prevention; D015854:Up-Regulation
D014408:Biomarkers, Tumor; C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D008565:Membrane Proteins; D012333:RNA, Messenger