title: Perivascular microenvironment in primary central nervous system lymphomas: the role of chemokines and the endothelin B receptor.
abstract: Chemokines are peptides that function as chemoattractant cytokines in cell activation, differentiation and trafficking. Endothelin B receptor (ETBR) is a receptor for endothelin, which is known to function as a vasoconstrictor. In the present study, to clarify the immune escape mechanism of primary central nervous system lymphomas (PCNSLs), the expression of ETBR and of subsets of chemokines (CXCL12, 13) in 24 PCNSLs was investigated. CXCL12 was expressed by lymphoma cells in different resident brain cell populations in 22/24 cases. CXCL13 expression was identified in tumor cells in 19/24 cases, but was only expressed by tumor cells and by proliferating vascular endothelial cells. In addition, tumor-infiltrated lymphocytes (TILs) accumulated in areas with expression of chemokines, particularly of CXCL13. ETBR expression was detected in 12/24 cases. Positive ETBR cases were associated with a paucity of TILs, particularly of cytotoxic T cells, whereas negative ETBR cases were associated with an abundance of TILs. The combined data indicate that CXCL12 and CXCL13 up-regulation may be differently linked to the development of PCNSLs and to the accumulation of TILs. In addition, ETBR expression by lymphoma and endothelial cells may mediate trafficking of TILs, which may explain the immune escape processes of PCNSLs.
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Asahimachi 67, Kurume, Fukuoka, 830-0011, Japan, sugita_yasuo@med.kurume-u.ac.jp.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Sugita
authors.forename: Mizuhiko
authors.initials: M
authors.lastname: Terasaki
authors.forename: Shinji
authors.initials: S
authors.lastname: Nakashima
authors.forename: Koichi
authors.initials: K
authors.lastname: Ohshima
authors.forename: Motohiro
authors.initials: M
authors.lastname: Morioka
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Abe
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016543:Central Nervous System Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D054377:Chemokine CXCL12 / Q000235:genetics / Q000502:physiology*; D054382:Chemokine CXCL13 / Q000235:genetics / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008223:Lymphoma / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D044023:Receptor, Endothelin B / Q000235:genetics / Q000502:physiology*; D019139:Tumor Escape / Q000235:genetics*; D059016:Tumor Microenvironment / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D054377:Chemokine CXCL12; D054382:Chemokine CXCL13; D044023:Receptor, Endothelin B