title: Expression of Tim-1 in primary CNS lymphoma.
abstract: Primary central nervous system lymphoma (PCNSL) is a distinct subtype of extranodal lymphoma with aggressive clinical course and poor outcome. As increased IL-10/IL-6 ratio is recognized in the cerebrospinal fluid (CSF) of PCNSL patients, we hypothesized that PCNSL might originate from a population of B cells with high IL-10-producing capacity, an equivalent of "regulatory B cells" in mice. We intended in this study to clarify whether Tim-1, a molecule known as a marker for regulatory B cells in mice, is expressed in PCNSL. By immunohistochemical analysis, Tim-1 was shown to be positive in as high as 54.2% of PCNSL (26 of 58 samples), while it was positive in 19.1% of systemic diffuse large B-cell lymphoma (DLBCL) samples (17 of 89 samples; P < 0.001). Tim-1 expression positively correlated with IL-10 expression in PCNSL (Cramer's V = 0.55, P < 0.001), and forced expression of Tim-1 in a PCNSL cell line resulted in increased IL-10 secretion, suggesting that Tim-1 is functionally linked with IL-10 production in PCNSL. Moreover, soluble Tim-1 was detectable in the CSF of PCNSL patients, and was suggested to parallel disease activity. In summary, PCNSL is characterized by frequent Tim-1 expression, and its soluble form in CSF may become a useful biomarker for PCNSL.
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Kishimoto
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Momoko
authors.initials: M
authors.lastname: Nishikori
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Arima
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Asahimachi, Kurume, Fukuoka, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Miyoshi
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Asahimachi, Kurume, Fukuoka, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Sasaki
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Kitawaki
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Shirakawa
authors.affiliation: Department of Hematology, Nagasaki University Hospital, Sakamoto, Nagasaki, Japan.
authors.forename: Takeharu
authors.initials: T
authors.lastname: Kato
authors.affiliation: Department of Hematology, Nagasaki University Hospital, Sakamoto, Nagasaki, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Imaizumi
authors.affiliation: Department of Hematology, Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Department of Hematology, Tenri Hospital, Mishima-cho, Tenri, Nara, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ohno
authors.affiliation: Department of Pathology, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Haga
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Asahimachi, Kurume, Fukuoka, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Ohshima
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Akifumi
authors.initials: A
authors.lastname: Takaori-Kondo
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D016543:Central Nervous System Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D030541:Databases, Genetic; D005260:Female; D015870:Gene Expression; D000072596:Hepatitis A Virus Cellular Receptor 1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008223:Lymphoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D015850:Interleukin-6; D016753:Interleukin-10
keywords: Biomarker; Tim-1; central nervous system; diffuse large B-cell lymphoma; immunohistochemistry