Expression and function of T cell homing molecules in Hodgkin's lymphoma.
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.
Machado
Lee
L
Cancer Research UK Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham, UK.
Jarrett
Ruth
R
Morgan
Susan
S
Murray
Paul
P
Hunter
Beatrix
B
Hamilton
Emma
E
Crocker
John
J
Thomas
Wendy
W
Steven
Neil
N
Ismail
Tariq
T
Chapman
Ann
A
Adams
David H
DH
Lee
Steven P
SP
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
D054387:Receptors, CXCR; D016201:Receptors, Lymphocyte Homing