Graft-versus-host disease after allogeneic hematopoietic stem cell transplantation induces a CD8+ T cell-mediated graft-versus-tumor effect that is independent of the recognition of alloantigenic tumor targets.
Cure of hematologic malignancies after allogeneic hematopoietic stem cell transplantation is partially attributable to immunocellular antitumor reactions termed graft-versus-tumor (GvT) effect. GvT effects are heterogeneous with respect to effector cell populations, target antigens, and their interrelation with graft-versus-host disease (GvHD). In the present study, allogeneic parent-into-F1 murine transplantation models (BALB/c or C57BL/6 --> [C57BL/6 x BALB/c]F1) with different tumors derived from either parental strain were used to evaluate tumor-specific GvT effects. Compared with syngeneic F1-into-F1 controls, significant CD8+ T cell-mediated GvT effects occurred in both allogeneic transplantation models, even in the absence of histoincompatibilities between donor cells and host tumor. Identical genetic background of donor and tumor precluded allorecognition of tumor cells, indicating that tumor-associated antigens (TAAs) were targeted. With allowance made for selective major histocompatibility complex (MHC) disparities between donor cells and normal host tissue, GvHD was identified as a driving force for TAA-specific GvT effects. Adoptive transfer of the effector cells into secondary tumor-bearing recipients confirmed sustained antitumor activity and specificity of the T-cell response. The results provide experimental proof of a donor CD8+ T cell-mediated TAA-specific antitumor response in vivo that is driven by GvHD. It may represent one of the mechanisms contributing to GvT effects observed in allogeneic transplant recipients.
Stelljes
Matthias
M
Department of Medicine/Hematology and Oncology, University of Münster, Albert-Schweitzer-Str 33, D-48129 Münster, Germany.
Strothotte
Robert
R
Pauels
Hans-Gerd
HG
Poremba
Christopher
C
Milse
Michaela
M
Specht
Christiane
C
Albring
Jörn
J
Bisping
Guido
G
Scheffold
Christian
C
Kammertoens
Thomas
T
Oelmann
Elisabeth
E
Silling
Gerda
G
Berdel
Wolfgang E
WE
Kienast
Joachim
J
D019264:Adoptive Transfer; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D020350:Graft vs Tumor Effect / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D007519:Isoantigens; D051379:Mice; D008815:Mice, Inbred Strains; D012509:Sarcoma / Q000628:therapy; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic; D016896:Treatment Outcome; D047368:Tumor Burden
D000951:Antigens, Neoplasm; D007519:Isoantigens