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 Running title: Tumor specific GvT reaction is driven by GvHD

Cure of hematological malignancies after allogeneic hematopoietic stem cell transplantation is partially attributable to immunocellular anti-tumor 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 transplant models (BALB/c or C57BL/6 -> F1[BALB/c x C57BL/6]) 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 transplant 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. Allowing for selective 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 anti-tumor activity and specificity of the T cell response. The results provide experimental proof of a donor CD8 T cell-mediated TAA-specific anti-tumor response in vivo that is driven by GvHD. It may represent one of the mechanisms contributing to GvT effects observed in allogeneic transplant recipients. For personal use only. on October 17, 2017. by guest www.bloodjournal.org From