High-Level Expression of Chemokine CXCL16 by Tumor Cells Correlates with a Good Prognosis and Increased Tumor-Infiltrating Lymphocytes in Colorectal Cancer

Abstract

CXCL16 is a new member of the chemokine superfamily, which exists in a transmembrane as well as a soluble form. Its receptor CXCR6 is detected on CD4 + T cells, CD8 + T cells, and natural killer T cells. Here, we report a significant correlation of CXCL16 expression by tumor cells with the infiltration of T cells and prognosis in colorectal cancer (CRC). We first found that CXCL16 expression was consistently up-regulated more in tumor tissues than in normal mucosa derived from the same CRC patients. Four human CRC cell lines also expressed CXCL16 mRNA and secreted soluble CXCL16. We next examined the expression of CXCL16 and infiltration of lymphocytes in CRC specimens (n = 58) by immunohistochemistry. CRC patients with high levels of CXCL16 expression (n = 43) had higher levels of CD4 + and CD8 + tumor-infiltrating lymphocytes (TIL; P < 0.01) than those with low levels of CXCL16 expression (n = 15). Furthermore, the high CXCL16 expression group showed significantly better prognosis than the low CXCL16 expression group (P < 0.05). Collectively, our data suggest that the expression of CXCL16 by tumor cells enhances the recruitment of TILs, thereby bringing about a better prognosis in CRC. Thus, CXCL16 is a new prognostic biomarker and may be useful for the development of a more effective therapeutic strategy for CRC. [Cancer Res 2007;67(10):4725-31]

Chemokines in cancer related inflammation

“…In human glioma, colorectal, breast and renal cancer, tumors with high CXCL16 expression had slower progression and showed infiltration of CD4 and CD8 lymphocytes [53][54][55][56][57]. On the contrary in prostate cancer CXCL16 expression has been correlated with poor prognosis [58].…”

Antitumor immune activity by chemokine CX3CL1 in an orthotopic implantation of lung cancer model in vivo

“…In breast cancer, a lower CCL2 expression was correlated with longer relapse-free survival and decreased tumor-associated macrophage (TAM) (24), while a higher level of CCL5 expression was associated with an increase of TAM and lymph node metastasis (25). In contrast to CCL2 and CCL5, a highlevel expression of chemokine CXCL16 by tumor cells has recently been reported to correlate with a good prognosis and increased CD8 + T as well as CD4 + T cells in CRC (26). In addition, CX3CL1 is correlated with a better prognosis and an increased number of CX3CR1-positive CD8 + T and NK cells migrated into primary cancer in several cancers, such as CRC (27) or gastric adenocarcinoma (28).…”

Reply to low expression of chloride channel accessory 1 predicts a poor prognosis in colorectal cancer: The question is still open

“…[3][4][5] Bonferroni correction is a method with which to counteract the problem of multiple comparisons. We applied the Bonferroni critical value (P <.0017) to examine the expression level of CLCA1 and CRC status in patients.…”