Depletion of CD25⺠T cells from hematopoietic stem cell grafts increases posttransplantation vaccine-induced immunity to neuroblastoma.
Blood
; 117(25): 6952-62, 2011 Jun 23.
Article
em En
| MEDLINE
| ID: mdl-21521781
ABSTRACT
A multifaceted immunotherapeutic strategy that includes hematopoietic stem cell (HSC) transplantation, T-cell adoptive transfer, and tumor vaccination can effectively eliminate established neuroblastoma tumors in mice. In vivo depletion of CD4⺠T cells in HSC transplantation recipients results in increased antitumor immunity when adoptively transferred T cells are presensitized, but development of T-cell memory is severely compromised. Because increased percentages of regulatory T (Treg) cells are seen in HSC transplantation recipients, here we hypothesized that the inhibitory effect of CD4⺠T cells is primarily because of the presence of expanded Treg cells. Remarkably, adoptive transfer of presensitized CD25-depleted T cells increased tumor vaccine efficacy. The enhanced antitumor effect achieved by ex vivo depletion of CD25⺠Treg cells was similar to that achieved by in vivo depletion of all CD4⺠T cells. Depletion of CD25⺠Treg cells resulted in elevated frequencies of tumor-reactive CD8 and CD4⺠T cells and increased CD8-to-Treg cell ratios inside tumor masses. All mice given presensitized CD25-depleted T cells survived a tumor rechallenge, indicating the development of long-term CD8⺠T-cell memory to tumor antigens. These observations should aid in the future design of immunotherapeutic approaches that promote the generation of both acute and long-term antitumor immunity.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
/
Imunoterapia Adotiva
/
Transplante de Células-Tronco Hematopoéticas
/
Vacinas Anticâncer
/
Subunidade alfa de Receptor de Interleucina-2
/
Neuroblastoma
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos