Specific central memory T cells in the bone marrow of patients immunized against tyrosinase peptides.
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-gamma 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.
Letsch
Anne
A
Department of Hematology, Oncology, and Transfusion Medicine, Charité, Campus Benjamin Franklin, Berlin, Germany.
Keilholz
Ulrich
U
Kern
Florian
F
Asemissen
Anne Marie
AM
Thiel
Eckhard
E
Scheibenbogen
Carmen
C
D001853:Bone Marrow / Q000276:immunology / Q000473:pathology; D019496:Cancer Vaccines; D017322:Clinical Trials, Phase II as Topic; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D008545:Melanoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D014442:Monophenol Monooxygenase / Q000737:chemistry / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D019496:Cancer Vaccines; D015395:Histocompatibility Antigens Class I; D014442:Monophenol Monooxygenase