Intratumoral IFN-α gene delivery reduces tumor-infiltrating regulatory T cells through the downregulation of tumor CCL17 expression.
Adenoviridae
/ genetics
Animals
Cell Line, Tumor
Chemokine CCL17
/ genetics
Disease Models, Animal
Female
Gene Expression
Gene Transfer Techniques
Genetic Therapy
Genetic Vectors
/ genetics
Humans
Interferon-alpha
/ genetics
Lymphocyte Count
Lymphocytes, Tumor-Infiltrating
/ immunology
Mice
Neoplasms
/ etiology
RNA, Small Interfering
/ genetics
T-Lymphocytes, Regulatory
/ immunology
Tumor Microenvironment
Xenograft Model Antitumor Assays
Journal
Cancer gene therapy
ISSN: 1476-5500
Titre abrégé: Cancer Gene Ther
Pays: England
ID NLM: 9432230
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
03
09
2018
accepted:
20
10
2018
revised:
12
10
2018
pubmed:
14
11
2018
medline:
7
7
2020
entrez:
14
11
2018
Statut:
ppublish
Résumé
The effect of IFN-α on the immunosuppressive tumor microenvironment is not fully understood. We previously reported that intratumoral IFN-α gene transduction decreased the frequency of regulatory T cells (Tregs) in the tumor by inducing the secretion of IL-6 from dendritic cells. In this study, we examined whether IFN-α affects the trafficking of Tregs to the tumor. Since CT26 cells expressed CCL17 among Treg-attracting chemokines, we focused on its role in IFN-α-mediated Treg suppression. IFN-α directly suppressed CCL17 production from CT26 cells in vitro, and IFN-α transduction reduced CCL17 expression in tumors in vivo. Next, to investigate whether CCL17 downregulation is related to the suppression of Treg trafficking, CCL17-downregulated CT26 cells produced using short hairpin RNA (CT26-shCCL17) were inoculated into mice. The frequency of Tregs in CT26-shCCL17 tumors was reduced and tumor growth was suppressed. Finally, to examine the combinatorial effect of IFN-α expression with CCL17 downregulation, IFN-α was transduced into CT26-shCCL17 tumors. This resulted in an elevation of CT26-specific CD8
Identifiants
pubmed: 30420718
doi: 10.1038/s41417-018-0059-5
pii: 10.1038/s41417-018-0059-5
doi:
Substances chimiques
CCL17 protein, human
0
Chemokine CCL17
0
Interferon-alpha
0
RNA, Small Interfering
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
334-343Références
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