title: Selective infiltration of CCR5(+)CXCR3(+) T lymphocytes in human colorectal carcinoma.
abstract: T cell infiltration in colorectal cancer is associated with a favorable prognosis, suggesting an occurrence of a certain degree of anti-tumor immunity. T helper type 1 (Th1) and Th2 cells are now known to selectively express CC-chemokine receptor 5 (CCR5)/CXC-chemokine receptor 3 (CXCR3) and CCR4, respectively. To clarify the mechanism of T cell infiltration, we examined in situ expression of these chemokine receptors and their respective chemokine ligands in 40 cases of human colorectal cancer. Immunohistochemistry showed a predominant accumulation of T cells expressing CCR5 and CXCR3 mainly along the invasive margin, whereas those expressing CCR4 were rare. Flow cytometric analysis showed that more than half of CD8(+) T cells and a fraction of CD4(+) cells isolated from fresh tumor tissues co-expressed CCR5 and CXCR3, and CD8(+) T cells and CD4(+) cells predominantly produced interferon-gamma (IFN-gamma) over interleukin-4 (IL-4) after in vitro stimulation. RANTES/CCL5, a ligand of CCR5, was localized within infiltrating CD8(+) T cells in a granular pattern, whereas IP-10/CXCL10, a ligand of CXCR3, was localized in cancer cells and macrophages along the invasive margin. These data were consistent with an active recruitment of T cells expressing CCR5 or CXCR3 into the invasive margin of colorectal cancer. With the previous clinicopathological studies showing a favorable prognostic impact of T cell infiltration in colorectal cancer, our study supports the occurrence of a certain level of Th1-shifted cellular immune responses in human colorectal cancer.
authors.affiliation: Department of Surgery, Tohoku University School of Medicine, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Musha
authors.forename: Haruo
authors.initials: H
authors.lastname: Ohtani
authors.forename: Takayuki
authors.initials: T
authors.lastname: Mizoi
authors.forename: Makoto
authors.initials: M
authors.lastname: Kinouchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakayama
authors.forename: Kennichi
authors.initials: K
authors.lastname: Shiiba
authors.forename: Kikuo
authors.initials: K
authors.lastname: Miyagawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagura
authors.forename: Osamu
authors.initials: O
authors.lastname: Yoshie
authors.forename: Iwao
authors.initials: I
authors.lastname: Sasaki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018925:Chemokines / Q000235:genetics; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000473:pathology; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008875:Middle Aged; D019713:Receptors, CCR5 / Q000235:genetics*; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: C515187:CXCR3 protein, human; D018925:Chemokines; D019713:Receptors, CCR5; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine