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, Steven 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-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.

Original languageEnglish
Pages (from-to)85-94
Number of pages10
JournalCancer Immunology, Immunotherapy
Volume58
Issue number1
DOIs
Publication statusPublished - Jan 2009
Externally publishedYes

Keywords

  • Chemokines
  • Hodgkin's lymphoma
  • T cell homing
  • Tumour Immunity

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