期刊
CANCER RESEARCH
卷 70, 期 9, 页码 3505-3514出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-09-4253
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- Associazione Italiana per la Ricerca sul Cancro and Ministero della Salute
- European Community [LSHC-CT-2005-018914]
Nonmyeloablative hematopoietic cell transplantation can cure patients with hematologic malignancies but has reported limited success against solid tumors. This is possibly because of profound peripheral tolerance mechanisms and/or suboptimal tumor recognition by effector T lymphocytes. We report that in mice developing spontaneous prostate cancer, nonmyeloablative minor histocompatibility mismatched hematopoietic stem cell transplantation, and donor lymphocyte infusion of unmanipulated lymphocytes combined with post-transplant tumor-specific vaccination circumvents tumor-specific tolerance, allowing acute tumor rejection and the establishment of protective immunosurveillance. Although donor-derived tumor-specific T cells readily differentiated into effector cells and infiltrated the tumor soon after infusion, they were alone insufficient for tumor eradication, which instead required the concomitance of minor histocompatibiltiy antigen-specific CD8(+) T-cell responses. The establishment of protective immunosurveillance was best induced by post-transplant tumor-specific vaccination. Hence, these results provide the proof of principle that tumor-specific T-cell responses have to be harnessed together with minor histocompatibility responses and sustained by post-transplant tumor-specific vaccination to improve the efficacy of allotransplantion for the cure of solid tumors. Cancer Res; 70( 9); 3505-14. (C) 2010 AACR.
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