Expression and function of T cell homing molecules in Hodgkin’s lymphoma

Lee Machado, Ruth Jarrett, Susan Morgan, Paul Murray, Beatrix Hunter, Emma Hamilton, John Crocker, Wendy Thomas, Neil Steven, Tariq Ismail, Ann Chapman, David H Adams, S P Lee

Research output: Contribution to JournalArticlepeer-review

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-inWltrating T cells in HL and compared them with T cells from unaVected 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 puriWed 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 unaVected 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.
Original languageEnglish
Pages (from-to)85–94
Number of pages10
JournalCancer Immunology, Immunotherapy
Volume58
Issue number1
Early online date17 May 2008
DOIs
Publication statusPublished - 1 Jan 2009

Keywords

  • Chemokines
  • Hodgkin’s lymphoma
  • T cell homing
  • tumour immunity

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