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

Cancer Immunol Immunother. 2009 Jan;58(1):85-94. doi: 10.1007/s00262-008-0528-z. Epub 2008 May 17.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Female
  • Flow Cytometry
  • Hodgkin Disease / immunology*
  • Hodgkin Disease / metabolism*
  • Hodgkin Disease / physiopathology
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Receptors, CXCR / immunology
  • Receptors, CXCR / metabolism
  • Receptors, Lymphocyte Homing / immunology
  • Receptors, Lymphocyte Homing / metabolism*
  • Young Adult

Substances

  • Receptors, CXCR
  • Receptors, Lymphocyte Homing