Concomitant tumor and minor histocompatibility antigen-specific immunity initiate rejection and maintain remission from established spontaneous solid tumors.

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 Res

journal_title

Cancer research

authors

Hess Michelini R,Freschi M,Manzo T,Jachetti E,Degl'Innocenti E,Grioni M,Basso V,Bonini C,Simpson E,Mondino A,Bellone M

doi

10.1158/0008-5472.CAN-09-4253

subject

Has Abstract

pub_date

2010-05-01 00:00:00

pages

3505-14

issue

9

eissn

0008-5472

issn

1538-7445

pii

0008-5472.CAN-09-4253

journal_volume

70

pub_type

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