title: Expression and function of T cell homing molecules in Hodgkin's lymphoma.
abstract: Circulating T lymphocytes enter a tissue if they express appropriate chemokine receptors and adhesion molecules to engage ligands presented at this site. To aid rational development of T cell-based therapies for Hodgkin's lymphoma (HL), we have assessed the expression and function of homing receptors on tumour-infiltrating T cells in HL and compared them with T cells from unaffected lymph nodes and colorectal cancer tissue. Chemokine receptors CXCR3, CXCR4 and CCR7 were expressed on a large proportion of T cells within HL tissue and mediated chemotaxis to purified chemokine. The corresponding ligands (CXCL10, CXCL12, CCL21) were expressed on the malignant cells and/or vascular endothelium. Adhesion molecules including CD62L were widely expressed on HL-derived T cells and their corresponding ligands were detected on vessels within the tumour. This homing phenotype was distinct from T cells isolated from colorectal cancer, but matched closely the phenotype of T cells from unaffected lymph nodes. Thus, T cell recruitment to HL resembles entry of naïve/central memory T cells into normal lymph nodes. This has important implications for current approaches to treat HL using T cells activated and expanded in vitro that lack CCR7 and CD62L expression.
authors.affiliation: Cancer Research UK Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham, UK.
authors.forename: Lee
authors.initials: L
authors.lastname: Machado
authors.forename: Ruth
authors.initials: R
authors.lastname: Jarrett
authors.forename: Susan
authors.initials: S
authors.lastname: Morgan
authors.forename: Paul
authors.initials: P
authors.lastname: Murray
authors.forename: Beatrix
authors.initials: B
authors.lastname: Hunter
authors.forename: Emma
authors.initials: E
authors.lastname: Hamilton
authors.forename: John
authors.initials: J
authors.lastname: Crocker
authors.forename: Wendy
authors.initials: W
authors.lastname: Thomas
authors.forename: Neil
authors.initials: N
authors.lastname: Steven
authors.forename: Tariq
authors.initials: T
authors.lastname: Ismail
authors.forename: Ann
authors.initials: A
authors.lastname: Chapman
authors.forename: David H
authors.initials: DH
authors.lastname: Adams
authors.forename: Steven P
authors.initials: SP
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D005260:Female; D005434:Flow Cytometry; D006689:Hodgkin Disease / Q000276:immunology* / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D054387:Receptors, CXCR / Q000276:immunology / Q000378:metabolism; D016201:Receptors, Lymphocyte Homing / Q000276:immunology / Q000378:metabolism*; D055815:Young Adult
chemical_list: D054387:Receptors, CXCR; D016201:Receptors, Lymphocyte Homing