Addition of GM-CSF to a peptide/KLH vaccine results in increased frequencies of CXCR3-expressing KLH-specific T cells.
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.
Na
Il-Kang
IK
Department of Hematology, Oncology and Transfusion Medicine, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany.
Keilholz
Ulrich
U
Letsch
Anne
A
Bauer
Sandra
S
Asemissen
Anne Marie
AM
Nagorsen
Dirk
D
Thiel
Eckhard
E
Scheibenbogen
Carmen
C
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D015331:Cohort Studies; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000276:immunology*; D006433:Hemocyanins / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D007271:Injections, Intradermal; D007279:Injections, Subcutaneous; D008545:Melanoma / Q000276:immunology* / Q000628:therapy; D009367:Neoplasm Staging; D010455:Peptides / Q000008:administration & dosage / Q000276:immunology*; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D000276:Adjuvants, Immunologic; C515187:CXCR3 protein, human; D019496:Cancer Vaccines; D010455:Peptides; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin