The Antitumor Efficacy of IL2/IL21-Cultured Polyfunctional Neu-Specific T Cells Is TNFα/IL17 Dependent.
Clin Cancer Res
; 22(9): 2207-16, 2016 05 01.
Article
em En
| MEDLINE
| ID: mdl-26660518
ABSTRACT
PURPOSE:
Infusion of HER2-specific T cells, derived from vaccine-primed patients and expanded with IL2/IL12, has induced tumor regression in a minority of patients with metastatic treatment-refractory HER2(+) breast cancer. We questioned whether alteration of cytokine growth factors used to culture vaccine-primed T cells could improve antitumor activity. EXPERIMENTALDESIGN:
Using the TgMMTV-neu murine mammary tumor model, we cultured T cells derived from mice immunized with a previously defined neu class II peptide, p98-114 (neu p98), and evaluated different cytokine combinations for expansion.RESULTS:
Infusion of neu p98-specific T-cell lines derived from all cytokine conditions evaluated resulted in significant antitumor activity compared with infused naïve splenocytes (P < 0.05). T cells cultured with IL2/IL21 could uniquely mediate complete regression of spontaneous mammary tumors. IL2/IL21 cultured neu-specific T cells demonstrated a different cytokine secretion pattern as compared with other cultured T cells; secreting high levels of TNFα and IL17 (P < 0.05). Moreover, tumor-infiltrating CD8(+) cells were significantly increased after the infusion of IL2/IL21 cultured T cells as compared with tumors treated with T cells expanded under other cytokine conditions (P < 0.001). The antitumor effect of the infusion of IL2/IL21 cultured cells was mediated by CD8 T cells. Depletion of TNFα or IL17, but not IFNγ, abrogated the tumor growth inhibition induced by the IL2/IL21 T cells and markedly decreased the influx of CD8 into tumors. Finally, IL2/IL21-cultured human antigen specific T cells also displayed a similar polyfunctional Th1/Th17 phenotype.CONCLUSIONS:
Expansion of HER2 vaccine-primed T cells with IL2/IL21 may have the potential to effectively mediate tumor regression when used in adoptive transfer. Clin Cancer Res; 22(9); 2207-16. ©2015 AACR.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos do Interstício Tumoral
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Interleucinas
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Interleucina-2
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Fator de Necrose Tumoral alfa
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Linfócitos T CD8-Positivos
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Interleucina-17
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Clin Cancer Res
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2016
Tipo de documento:
Article