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Publication : Vaccine-instructed intratumoral IFN-γ enables regression of autochthonous mouse prostate cancer in allogeneic T-cell transplantation.

First Author  Hess Michelini R Year  2013
Journal  Cancer Res Volume  73
Issue  15 Pages  4641-52
PubMed ID  23749644 Mgi Jnum  J:199470
Mgi Id  MGI:5502822 Doi  10.1158/0008-5472.CAN-12-3464
Citation  Hess Michelini R, et al. (2013) Vaccine-Instructed Intratumoral IFN-gamma Enables Regression of Autochthonous Mouse Prostate Cancer in Allogeneic T-Cell Transplantation. Cancer Res 73(15):4641-52
abstractText  Vaccination can synergize with transplantation of allogeneic hematopoietic stem cells to cure hematologic malignancies, but the basis for this synergy is not understood to the degree where such approaches could be effective for treating solid tumors. We investigated this issue in a transgenic mouse model of prostate cancer treated by transplantation of a nonmyeloablative MHC-matched, single Y chromosome-encoded, or multiple minor histocompatibility antigen-mismatched hematopoietic cell preparation. Here, we report that tumor-directed vaccination after allogeneic hematopoietic stem cell transplantation and donor lymphocyte infusion is essential for acute graft versus tumor responses, tumor regression, and prolonged survival. Vaccination proved essential for generation of CD8(+) IFN-gamma(+) tumor-directed effector cells in secondary lymphoid organs and also for IFN-gamma(+) upregulation at the tumor site, which in turn instructed local expression of proinflammatory chemokines and intratumoral recruitment of donor-derived T cells for disease regression. Omitting vaccination, transplanting IFN-gamma-deficient donor T cells, or depleting alloreactive T cells all compromised intratumoral IFN-gamma-driven inflammation and lymphocyte infiltration, abolishing antitumor responses and therapeutic efficacy of the combined approach. Our findings argue that posttransplant tumor-directed vaccination is critical to effectively direct donor T cells to the tumor site in cooperation with allogeneic hematopoietic cell transplantation. Cancer Res; 73(00); 4641-52. (c)2013 AACR.
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