CD8+T cell-specific induction of NKG2D receptor by doxorubicin plus interleukin-12 and its contribution to CD8+T cell accumulation in tumors.
Mol Cancer
; 13: 34, 2014 Feb 24.
Article
em En
| MEDLINE
| ID: mdl-24565056
ABSTRACT
BACKGROUND:
Increased infiltration of CD8+T cells into tumors has a positive impact on survival. Our previous study showed that doxorubicin (Dox) plus interleukin-12 (IL-12) boosted the accumulation of CD8+T cells in tumors and had a greater antitumor effect than did either agent alone. The purpose of this study was to determine the impact of NKG2D expression on CD8+T cell infiltration and antitumor efficacy.METHODS:
Tumor-bearing mice were administered Dox, IL-12 plasmid DNA, or both via intraperitoneal injection or intramuscular electroporation. The induction of NKG2D on CD8+T cells and other lymphocytes was analyzed via flow cytometry, and NKG2D-positive CD8+T cell-specific localization in tumors was determined by using immunofluorescence staining in various types of immune cell-depleted mice.RESULTS:
The combination of Dox plus IL-12 specifically increased expression of NKG2D in CD8+T cells but not in other types of immune cells, including NK cells, which naturally express NKG2D. This induced NKG2D expression in CD8+T cells was associated with increased accumulation of CD8+T cells in murine tumors. Administration of NKG2D-blocking antibody or CD8+T cell-depletion antibody abrogated the NKG2D+CD8+T cell detection in tumors, whereas administration of NK cell-depletion antibody had no effect. Increased NKG2D expression in CD8+T cells was associated with increased antitumor efficacy in vivo.CONCLUSION:
We conclude that Dox plus IL-12 induces NKG2D in CD8+T cells in vivo and boosts NKG2D+CD8+T-dependent antitumor immune surveillance. This discovery reveals a novel mechanism for how chemoimmunotherapy synergistically promotes T cell-mediated antitumor immune surveillance.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Protocolos de Quimioterapia Combinada Antineoplásica
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Linfócitos do Interstício Tumoral
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Linfócitos T CD8-Positivos
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Subfamília K de Receptores Semelhantes a Lectina de Células NK
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Neoplasias Mamárias Experimentais
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article