Abstract:
: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 posttransplant 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 posttransplant 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 posttransplant tumor-specific vaccination to improve the efficacy of allotransplantion for the cure of solid tumors.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Hess Michelini R,Freschi M,Manzo T,Jachetti E,Degl'Innocenti E,Grioni M,Basso V,Bonini C,Simpson E,Mondino A,Bellone Mdoi
10.1158/0008-5472.CAN-09-4253subject
Has Abstractpub_date
2010-05-01 00:00:00pages
3505-14issue
9eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-09-4253journal_volume
70pub_type
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