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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

Item Type:Article
Title: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
Creators Name:Stelljes, M. and Strothotte, R. and Pauels, H.G. and Poremba, C. and Milse, M. and Specht, C. and Albring, J. and Bisping, G. and Scheffold, C. and Kammertoens, T. and Oelmann, E. and Silling, G. and Berdel, W.E. and Kienast, J.
Abstract: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 × 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.
Keywords:Adoptive Transfer, CD8-Positive T-Lymphocytes, Graft vs Host Disease, Graft vs Tumor Effect, Hematopoietic Stem Cell Transplantation, Homologous Transplantation, Inbred Strains Mice, Isoantigens, Isogeneic Transplantation, Neoplasm Antigens, Sarcoma, Treatment Outcome, Tumor Burden, Animals, Mice
Source:Blood
ISSN:0006-4971
Publisher:American Society of Hematology (U.S.A.)
Volume:104
Number:4
Page Range:1210-1216
Date:1 January 2004
Official Publication:https://doi.org/10.1182/blood-2003-10-3387
PubMed:View item in PubMed

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