Specifically activated memory T cell subsets from cancer patients recognize and reject xenotransplanted autologous tumors.
Bone marrow of breast cancer patients was found to contain CD8(+) T cells specific for peptides derived from breast cancer-associated proteins MUC1 and Her-2/neu. Most of these cells had a central or effector memory phenotype (CD45RA(-)CD62L(+) or CD45RA(-)CD62L(-), respectively). To test their in vivo function, we separated bone marrow-derived CD45RA(+) naive or CD45RA(-)CD45RO(+) memory T cells, stimulated them with autologous dendritic cells pulsed with tumor lysate, and transferred them into NOD/SCID mice bearing autologous breast tumors and normal skin transplants. CD45RA(-) memory but not CD45RA(+) naive T cells infiltrated autologous tumor but not skin tissues after the transfer. These tumor-infiltrating cells had a central or effector memory phenotype and produced perforin. Many of them expressed the P-selectin glycoprotein ligand 1 and were found around P-selectin(+) tumor endothelium. Tumor infiltration included cluster formation in tumor tissue by memory T cells with cotransferred dendritic cells. It was associated with the induction of tumor cell apoptosis and significant tumor reduction. We thus demonstrate selective homing of memory T cells to human tumors and suggest that tumor rejection is based on the recognition of tumor-associated antigens on tumor cells and dendritic cells by autologous specifically activated central and effector memory T cells.
Beckhove
Philipp
P
Division of Cellular Immunology, Tumor Immunology Program, German Cancer Research Center, Heidelberg, Germany.
Feuerer
Markus
M
Dolenc
Mathias
M
Schuetz
Florian
F
Choi
Carmen
C
Sommerfeldt
Nora
N
Schwendemann
Jochen
J
Ehlert
Katrin
K
Altevogt
Peter
P
Bastert
Gunther
G
Schirrmacher
Volker
V
Umansky
Viktor
V
D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D001854:Bone Marrow Cells / Q000276:immunology / Q000473:pathology; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009368:Neoplasm Transplantation / Q000276:immunology; D009369:Neoplasms / Q000276:immunology*; D012016:Reference Values; D016019:Survival Analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014183:Transplantation, Heterologous / Q000276:immunology*
D015703:Antigens, CD