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Microwave ablation combined with OK-432 induces Th1-type response and specific antitumor immunity in a murine model of breast cancer
BACKGROUND: Minimally invasive therapies, such as microwave ablation (MWA), are widely used for the treatment of solid tumors. Previous studies suggest that MWA is feasible for the treatment of small breast cancer, and thermal ablation may induce adaptive antitumor immunity. However, the induced imm...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5282633/ https://www.ncbi.nlm.nih.gov/pubmed/28137271 http://dx.doi.org/10.1186/s12967-017-1124-9 |
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author | Li, Li Wang, Wei Pan, Hong Ma, Ge Shi, Xinyi Xie, Hui Liu, Xiaoan Ding, Qiang Zhou, Wenbin Wang, Shui |
author_facet | Li, Li Wang, Wei Pan, Hong Ma, Ge Shi, Xinyi Xie, Hui Liu, Xiaoan Ding, Qiang Zhou, Wenbin Wang, Shui |
author_sort | Li, Li |
collection | PubMed |
description | BACKGROUND: Minimally invasive therapies, such as microwave ablation (MWA), are widely used for the treatment of solid tumors. Previous studies suggest that MWA is feasible for the treatment of small breast cancer, and thermal ablation may induce adaptive antitumor immunity. However, the induced immune responses are mostly weak, and the immunomodulation effects of MWA in breast cancer are unclear. Immunostimulant OK-432 can induce tumor-specific T-cell responses and may augment the immunity induced by MWA. METHODS: We treated 4T1 breast cancer bearing BALB/c mice with MWA, OK-432, MWA plus OK-432, or left without treatment. Survival time was evaluated with the Kaplan–Meyer method comparing survival curves by log-rank test. On day 25 after ablation, surviving mice received tumor rechallenge, and the rechallenged tumor volumes were calculated every 5 days. Immunohistochemistry and flow cytometry were used to evaluate the T-cell immune responses in ablated tissues and spleens. The tumor-specific immunity was assessed by enzyme-linked immunospot assays. Besides, the cytokine patterns were identified from enzyme-linked immunosorbent assay. RESULTS: Microwave ablation plus OK-432 resulted in longer survival than single treatment and protect most surviving mice from tumor rechallenge. Both local and systemic T-cell responses were induced by MWA and were further enhanced by subsequent administration of OK-432. Moreover, the combination of MWA and OK-432 induced stronger tumor-specific immune responses than MWA alone. In addition, OK-432 and MWA synergistically promoted the production of Th1-type but not Th2-type cytokines, and polarized T-cell responses to Th1-dominant state. CONCLUSIONS: The T-cell immune responses were activated by MWA in breast cancer. Furthermore, the combination of MWA and OK-432 induced Th1-type response and elicited specific antitumor immunity. |
format | Online Article Text |
id | pubmed-5282633 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-52826332017-02-03 Microwave ablation combined with OK-432 induces Th1-type response and specific antitumor immunity in a murine model of breast cancer Li, Li Wang, Wei Pan, Hong Ma, Ge Shi, Xinyi Xie, Hui Liu, Xiaoan Ding, Qiang Zhou, Wenbin Wang, Shui J Transl Med Research BACKGROUND: Minimally invasive therapies, such as microwave ablation (MWA), are widely used for the treatment of solid tumors. Previous studies suggest that MWA is feasible for the treatment of small breast cancer, and thermal ablation may induce adaptive antitumor immunity. However, the induced immune responses are mostly weak, and the immunomodulation effects of MWA in breast cancer are unclear. Immunostimulant OK-432 can induce tumor-specific T-cell responses and may augment the immunity induced by MWA. METHODS: We treated 4T1 breast cancer bearing BALB/c mice with MWA, OK-432, MWA plus OK-432, or left without treatment. Survival time was evaluated with the Kaplan–Meyer method comparing survival curves by log-rank test. On day 25 after ablation, surviving mice received tumor rechallenge, and the rechallenged tumor volumes were calculated every 5 days. Immunohistochemistry and flow cytometry were used to evaluate the T-cell immune responses in ablated tissues and spleens. The tumor-specific immunity was assessed by enzyme-linked immunospot assays. Besides, the cytokine patterns were identified from enzyme-linked immunosorbent assay. RESULTS: Microwave ablation plus OK-432 resulted in longer survival than single treatment and protect most surviving mice from tumor rechallenge. Both local and systemic T-cell responses were induced by MWA and were further enhanced by subsequent administration of OK-432. Moreover, the combination of MWA and OK-432 induced stronger tumor-specific immune responses than MWA alone. In addition, OK-432 and MWA synergistically promoted the production of Th1-type but not Th2-type cytokines, and polarized T-cell responses to Th1-dominant state. CONCLUSIONS: The T-cell immune responses were activated by MWA in breast cancer. Furthermore, the combination of MWA and OK-432 induced Th1-type response and elicited specific antitumor immunity. BioMed Central 2017-01-31 /pmc/articles/PMC5282633/ /pubmed/28137271 http://dx.doi.org/10.1186/s12967-017-1124-9 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Li, Li Wang, Wei Pan, Hong Ma, Ge Shi, Xinyi Xie, Hui Liu, Xiaoan Ding, Qiang Zhou, Wenbin Wang, Shui Microwave ablation combined with OK-432 induces Th1-type response and specific antitumor immunity in a murine model of breast cancer |
title | Microwave ablation combined with OK-432 induces Th1-type response and specific antitumor immunity in a murine model of breast cancer |
title_full | Microwave ablation combined with OK-432 induces Th1-type response and specific antitumor immunity in a murine model of breast cancer |
title_fullStr | Microwave ablation combined with OK-432 induces Th1-type response and specific antitumor immunity in a murine model of breast cancer |
title_full_unstemmed | Microwave ablation combined with OK-432 induces Th1-type response and specific antitumor immunity in a murine model of breast cancer |
title_short | Microwave ablation combined with OK-432 induces Th1-type response and specific antitumor immunity in a murine model of breast cancer |
title_sort | microwave ablation combined with ok-432 induces th1-type response and specific antitumor immunity in a murine model of breast cancer |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5282633/ https://www.ncbi.nlm.nih.gov/pubmed/28137271 http://dx.doi.org/10.1186/s12967-017-1124-9 |
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