title: 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.
authors.affiliation: Department of Surgery (II), Institute of Natural Medicine, University of Toyama, Toyama, Japan.
authors.forename: Shozo
authors.initials: S
authors.lastname: Hojo
authors.forename: Keiichi
authors.initials: K
authors.lastname: Koizumi
authors.forename: Koichi
authors.initials: K
authors.lastname: Tsuneyama
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Arita
authors.forename: Zhengguo
authors.initials: Z
authors.lastname: Cui
authors.forename: Kanna
authors.initials: K
authors.lastname: Shinohara
authors.forename: Takayuki
authors.initials: T
authors.lastname: Minami
authors.forename: Isaya
authors.initials: I
authors.lastname: Hashimoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakayama
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sakurai
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takano
authors.forename: Osamu
authors.initials: O
authors.lastname: Yoshie
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tsukada
authors.forename: Ikuo
authors.initials: I
authors.lastname: Saiki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051116:Receptors, Scavenger / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology*
chemical_list: C423727:CXCL16 protein, human; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D012333:RNA, Messenger; D051116:Receptors, Scavenger