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Cancer Immunol Res. 2013 Nov;1(5):332-9. doi: 10.1158/2326-6066.CIR-13-0084.

Peptide vaccination in Montanide adjuvant induces and GM-CSF increases CXCR3 and cutaneous lymphocyte antigen expression by tumor antigen-specific CD8 T cells.

Author information

1
Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756 ; Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756.
2
Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA 22908.
3
Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756.
4
Department of Surgery, University of Virginia School of Medicine, Charlottesville, VA 22908.

Abstract

T cell infiltration of melanoma is associated with enhanced clinical efficacy and is a desirable endpoint of immunotherapeutic vaccination. Infiltration is regulated, in part, by chemokine receptors and selectin ligands on the surface of tumor-specific lymphocytes. Therefore, we investigated the expression of two homing molecules--CXCR3 and CLA - on vaccine-induced CD8 T cells, in the context of a clinical trial of a melanoma-specific peptide vaccine. Both CXCR3 and CLA have been associated with T cell infiltration of melanoma. We demonstrate that a single subcutaneous/intradermal administration of peptide vaccine in Montanide adjuvant induces tumor-specific CD8 T cells that are predominantly positive for CXCR3, with a subpopulation of CXCR3(+)CLA(+) cells. Addition of GM-CSF significantly enhances CXCR3 expression and increases the proportion of CLA-expressing cells. Concurrent with CXCR3 and CLA expression, vaccine-induced CD8 cells express high levels of Tbet, IFN-γ, and IL-12Rβ1. Collectively, these studies demonstrate that peptide vaccination in adjuvant induces CD8 T cells with a phenotype that may support infiltration of melanoma.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00089193.

KEYWORDS:

CLA; CXCR3; GM-CSF; IL-12R; adjuvant; melanoma; peptide vaccines

PMID:
24377099
PMCID:
PMC3873151
DOI:
10.1158/2326-6066.CIR-13-0084
[Indexed for MEDLINE]
Free PMC Article

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