Peptide vaccination in montanide adjuvant induces and GM-CSF increases CXCR3 and cutaneous lymphocyte antigen expression by tumor antigen–specific CD8 T …

E Clancy-Thompson, LK King, LD Nunnley… - Cancer immunology …, 2013 - AACR
E Clancy-Thompson, LK King, LD Nunnley, IM Mullins, CL Slingluff Jr, DW Mullins
Cancer immunology research, 2013AACR
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, CXC chemokine
receptor 3 (CXCR3) and cutaneous lymphocyte antigen (CLA), on vaccine-induced CD8 T
cells, in the context of a clinical trial of a melanoma-specific peptide vaccine. Both CXCR3 …
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, CXC chemokine receptor 3 (CXCR3) and cutaneous lymphocyte antigen (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 show 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 granulocyte macrophage colony—stimulating factor (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 T-bet, IFN-γ, and interleukin-12 receptor (IL-12Rβ1). Collectively, these studies show that peptide vaccination in adjuvant induces CD8 T cells with a phenotype that may support infiltration of melanoma. Cancer Immunol Res; 1(5); 332–9. ©2013 AACR.
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