Specific Central Memory T Cells in the Bone Marrow of Patients Immunized Against Tyrosinase Peptides

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Abstract
The goal of vaccination against tumors is the induction of effector T cells mediating tumor destruction and memory T cells providing long-term immunity. Several previous studies in patients vaccinated with major histocompatibility complex (MHC) class I peptides failed to show induction of central memory T cells, which are considered important to provide long-term memory. This study examined the subset composition and function of specific T cells generated by immunization with MHC class I binding tyrosinase peptides in combination with the adjuvants granulocyte-macrophage colony-stimulating factor and keyhole limpet hemocyanin in peripheral blood (PB) and bone marrow (BM) of melanoma patients. Most of the tyrosinase-specific T cells in PB had a CD45RA+CCR7− effector phenotype. In contrast to this, a large subset of tyrosinase-specific T cells in BM were memory T cells, including CD45RA−CCR7+ central and CD45RA−CCR7− effector memory T cells. BM tyrosinase-specific T cells were functional, because they produced interferon-γ and had a high proliferative potential. This study suggests that peptide vaccination can generate a fully functional memory T-cell response characterized by central and effector memory phenotypes, proliferative potential, and BM tropism.

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