The therapeutic T-cell response induced by tumor delivery of TNF and melphalan is dependent on early triggering of natural killer and dendritic cells.
Eur J Immunol
; 47(4): 743-753, 2017 04.
Article
en En
| MEDLINE
| ID: mdl-28198545
ABSTRACT
The fusion protein L19mTNF (mouse TNF and human antibody fragment L19 directed to fibronectin extra domain B) selectively targets the tumor vasculature, and in combination with melphalan induces a long-lasting T-cell therapeutic response and immune memory in murine models. Increasing evidence suggests that natural killer (NK) cells act to promote effective T-cell-based antitumor responses. We have analyzed the role of NK cells and dendritic cells (DCs) on two different murine tumor models WEHI-164 fibrosarcoma and C51 colon carcinoma, in which the combined treatment induces high and low rejection rates, respectively. In vivo NK-cell depletion strongly reduced the rejection of WEHI-164 fibrosarcoma and correlated with a decrease in mature DCs, CD4+ , and CD8+ T cells in the tumor-draining LNs and mature DCs and CD4+ T cells in the tumor 40 h after initiation of the therapy. NK-cell depletion also resulted in the impairment of the stimulatory capability of DCs derived from tumor-draining LNs of WEHI-164-treated mice. Moreover, a significant reduction of M2-type infiltrating macrophages was detected in both tumors undergoing therapy. These results suggest that the efficacy of L19mTNF/melphalan therapy is strongly related to the early activation of NK cells and DCs, which are necessary for an effective T-cell response.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Dendríticas
/
Proteínas Recombinantes de Fusión
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Células Asesinas Naturales
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Linfocitos T Citotóxicos
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Neoplasias Colorrectales
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Linfocitos T CD4-Positivos
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Antineoplásicos Alquilantes
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Quimioterapia Combinada
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Fibrosarcoma
/
Melfalán
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Eur J Immunol
Año:
2017
Tipo del documento:
Article
País de afiliación:
Italia