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BMC Cancer. 2015 Oct 15;15:708. doi: 10.1186/s12885-015-1690-2.

Improving immunological tumor microenvironment using electro-hyperthermia followed by dendritic cell immunotherapy.

Author information

1
Department of Radiation Oncology, Chiayi Christian Hospital, Chiayi, Taiwan. radonco@yahoo.com.
2
Department of Biomedical Engineering, Chung Yuan Christian University, Taoyuan City, Taiwan. radonco@yahoo.com.
3
Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. chengchung2011@gmail.com.
4
Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. M011360@ms.skh.org.tw.
5
Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. michal0806@gmail.com.
6
Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. r95629018@gmail.com.
7
Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. yusam.wang@gmail.com.
8
Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan. gandocs@gmail.com.
9
Department of Biotechnics, St. Istvan University, Budapest, Hungary. Andras.Szasz@oncotherm.com.
10
Department of Biomedical Engineering, Chung Yuan Christian University, Taoyuan City, Taiwan. wtli@cycu.edu.tw.
11
Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. M006565@ms.skh.org.tw.
12
Institute of Radiation Science and School of Medicine, National Yang-Ming University, Taipei, Taiwan. M006565@ms.skh.org.tw.

Abstract

BACKGROUND:

The treatment of intratumoral dentritic cells (DCs) commonly fails because it cannot evoke immunity in a poor tumor microenvironment (TME). Modulated electro-hyperthermia (mEHT, trade-name: oncothermia) represents a significant technological advancement in the hyperthermia field, allowing the autofocusing of electromagnetic power on a cell membrane to generate massive apoptosis. This approach turns local immunogenic cancer cell death (apoptosis) into a systemic anti-tumor immune response and may be implemented by treatment with intratumoral DCs.

METHODS:

The CT26 murine colorectal cancer model was used in this investigation. The inhibition of growth of the tumor and the systemic anti-tumor immune response were measured. The tumor was heated to a core temperature of 42 °C for 30 min. The matured synergetic DCs were intratumorally injected 24 h following mEHT was applied.

RESULTS:

mEHT induced significant apoptosis and enhanced the release of heat shock protein70 (Hsp70) in CT26 tumors. Treatment with mEHT-DCs significantly inhibited CT26 tumor growth, relative to DCs alone or mEHT alone. The secondary tumor protection effect upon rechallenging was observed in mice that were treated with mEHT-DCs. Immunohistochemical staining of CD45 and F4/80 revealed that mEHT-DC treatment increased the number of leukocytes and macrophages. Most interestingly, mEHT also induced infiltrations of eosinophil, which has recently been reported to be an orchestrator of a specific T cell response. Cytotoxic T cell assay and ELISpot assay revealed a tumor-specific T cell activity.

CONCLUSIONS:

This study demonstrated that mEHT induces tumor cell apoptosis and enhances the release of Hsp70 from heated tumor cells, unlike conventional hyperthermia. mEHT can create a favorable tumor microenvironment for an immunological chain reaction that improves the success rate of intratumoral DC immunotherapy.

PMID:
26472466
PMCID:
PMC4608323
DOI:
10.1186/s12885-015-1690-2
[Indexed for MEDLINE]
Free PMC Article

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