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.

• Authors: Rodrigo Hess Michelini, Massimo Freschi, Teresa Manzo, Elena Jachetti, Elena Degl'Innocenti, Matteo Grioni, Veronica Basso, Chiara Bonini, Elizabeth Simpson, Anna Mondino, Matteo Bellone
• Journal: Cancer research (Cancer Res) Vol. 70 Issue 9 Pg. 3505-14 (May 01 2010) ISSN: 1538-7445 [Electronic] United States
• PMID: 20388780 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c)2010 AACR.

Chemical References

• Antigens, Bacterial
• Cancer Vaccines
• Epitopes
• Epitopes, T-Lymphocyte
• H antigen

Topics

• Animals
• Antigens, Bacterial (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Cancer Vaccines (immunology, pharmacology)
• Disease-Free Survival
• Epitopes
• Epitopes, T-Lymphocyte (immunology)
• Female
• Hematopoietic Stem Cell Transplantation
• Immunotherapy, Adoptive
• Lymphocyte Transfusion
• Lymphocytes (immunology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Prostatic Neoplasms (immunology, therapy)