Addition of GM-CSF to a peptide/KLH vaccine results in increased frequencies of CXCR3-expressing KLH-specific T cells

Cancer Immunol Immunother. 2007 Mar;56(3):391-6. doi: 10.1007/s00262-006-0198-7. Epub 2006 Jul 19.

Abstract

T-cell trafficking is determined by expression patterns of chemokine receptors. The chemokine receptor CXCR3 is expressed on a subpopulation of type 1 T cells and plays an important role for migration of T cells into inflamed and tumor tissues. Here, we studied the chemokine receptor expression on specific T cells generated against the neoantigen keyhole limpet hemocyanin (KLH) in patients who had been immunized in the context of a tumor peptide vaccination trial with or without the adjuvant granulocyte-macrophage colony-stimulating factor (GM-CSF). In patients immunized in the presence of GM-CSF the fraction of CXCR3(+) KLH-specific T cells was significantly higher than in patients immunized in the absence of GM-CSF (median 45 vs. 20%, P = 0.001). In contrast, the chemokine receptor CCR4, associated with migration to the skin was found in both cohorts on less than 10% of KLH-specific T cells. These results show that CXCR3 expression on vaccine-induced T cells can be modulated by modifying the local vaccine milieu.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Cancer Vaccines / immunology*
  • Cancer Vaccines / therapeutic use
  • Cell Line, Tumor
  • Cohort Studies
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology*
  • Hemocyanins / administration & dosage
  • Hemocyanins / immunology*
  • Humans
  • Injections, Intradermal
  • Injections, Subcutaneous
  • Melanoma / immunology*
  • Melanoma / therapy
  • Neoplasm Staging
  • Peptides / administration & dosage
  • Peptides / immunology*
  • Receptors, CXCR3
  • Receptors, Chemokine / biosynthesis*
  • Receptors, Chemokine / immunology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*

Substances

  • Adjuvants, Immunologic
  • CXCR3 protein, human
  • Cancer Vaccines
  • Peptides
  • Receptors, CXCR3
  • Receptors, Chemokine
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Hemocyanins
  • keyhole-limpet hemocyanin