Induction of type I IFN is required for overcoming tumor-specific T-cell tolerance after stem cell transplantation.

Published

Journal Article

Tumor-specific T-cell tolerance represents one major mechanism of tumor-induced immune evasion. Myeloablative chemotherapy with stem cell transplantation may offer the best chance of achieving a state of minimal residual disease and, thus, minimize tumor-induced immune evasion. However, studies have shown that tumor-specific T-cell tolerance persists after transplantation. Here, we showed that CD4(+)CD25(+) regulatory T (T(Reg)) cells play a critical role in tumor-specific CD8(+) T-cell tolerance after transplantation. Removal of T(Reg) cells from the donor lymphocyte graft did not overcome this tolerance because of rapid conversion of donor CD4(+)CD25(-) T cells into CD4(+)CD25(+)Foxp3(+) T(Reg) cells in recipients after transplantation, and depletion of T(Reg) cells in recipients was necessary for the reversal of tumor-specific tolerance. These results suggest that strategies capable of overcoming T-cell tolerance in recipients are required to promote antitumor immunity after transplantation. Toward this goal, we showed that dendritic cell (DC) vaccines coadministered with the TLR9 ligand, CpG could effectively overcome tumor-specific tolerance, leading to significant prolongation of tumor-free survival after transplantation. We further showed that CpG-induced type I interferon was critical for the reversal of tumor-specific tolerance in vivo. Collectively, these results may suggest effective immunotherapeutic strategies for treating cancer after stem cell transplantation.

Full Text

Duke Authors

Cited Authors

  • Horkheimer, I; Quigley, M; Zhu, J; Huang, X; Chao, NJ; Yang, Y

Published Date

  • May 21, 2009

Published In

Volume / Issue

  • 113 / 21

Start / End Page

  • 5330 - 5339

PubMed ID

  • 19279333

Pubmed Central ID

  • 19279333

Electronic International Standard Serial Number (EISSN)

  • 1528-0020

Digital Object Identifier (DOI)

  • 10.1182/blood-2008-05-155150

Language

  • eng

Conference Location

  • United States