Abscopal antitumor immune effects of magnet‑mediated hyperthermia at a high therapeutic temperature on Walker‑256 carcinosarcomas in rats

Wang,Hui; Zhang,Li; Shi,Yingrui; Javidiparsijani,Sara; Wang,Guirong; Li,Xiao; Ouyang,Weiwei; Zhou,Jumei; Zhao,Lingyun; Wang,Xiaowen; Zhang,Xiaodong; Gao,Fuping; Liu,Jingshi; Luo,Junming; Tang,Jintian

doi:10.3892/ol.2014.1803

Abscopal antitumor immune effects of magnet‑mediated hyperthermia at a high therapeutic temperature on Walker‑256 carcinosarcomas in rats

Authors:
- Hui Wang
- Li Zhang
- Yingrui Shi
- Sara Javidiparsijani
- Guirong Wang
- Xiao Li
- Weiwei Ouyang
- Jumei Zhou
- Lingyun Zhao
- Xiaowen Wang
- Xiaodong Zhang
- Fuping Gao
- Jingshi Liu
- Junming Luo
- Jintian Tang
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Affiliations: Department of Radiation Oncology, The Affiliated Hunan Provincial Tumor Hospital of Xiangya Medical School, Central South University, Changsha, Hunan 410013, P.R. China, Department of Engineering Physics, Tsinghua University Key Laboratory of Particle and Radiation Imaging, Ministry of Education, Haidian, Beijing 100084, P.R. China, Department of Surgery, SUNY Upstate Medical University, Syracuse, NY 13210, USA, Department of Radiation Oncology, The Affiliated Xiangya Hospital of Xiangya Medical School, Central South University, Changsha, Hunan 410013, P.R. China, Department of Thoracic Oncology, Guizhou Cancer Hospital, Guiyang, Guizhou 550004, P.R. China, Department of Anesthesiology, Hunan Provincial Tumor Hospital, The Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, Hunan 410013, P.R. China
Published online on: January 15, 2014 https://doi.org/10.3892/ol.2014.1803
Pages: 764-770

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Abstract

The abscopal effect has previously been described in various tumors and is associated with radiation therapy and hyperthermia, with possible underlying mechanisms explaining each observed case. In the present study, we aimed to investigate the antitumor effects of magnet‑mediated hyperthermia on Walker‑256 carcinosarcomas in rats at two different temperature ranges (42‑46˚C and 50‑55˚C). We also aimed to identify whether a higher therapeutic temperature of magnetic‑mediated hyperthermia improves the abscopal antitumor effects, where localised irradiation of the tumor causes not only the irradiated tumor to shrink, but also tumors located far from the area of irradiation. Following induction of carcinosarcoma in both sides of the body, magnet‑mediated hyperthermia was applied to one side only, leaving the other side as a control. The changes in tumor growth were observed. Our results demonstrated that magnet‑mediated hyperthermia at a higher temperature inhibited the growth of carcinosarcoma at the site of treatment. Furthermore, the growth of the carcinosarcoma on the untreated side was also inhibited. The expression levels of proliferating cell nuclear antigen were decreased in the hyperthermia group, which was more significant in the higher temperature test group. Flow cytometric analysis showed an increased number of CD4‑ and CD8‑positive T cells, and enzyme‑linked immunosorbent assay showed increased levels of interferon‑γ and interleukin‑2 in the higher temperature group. These results suggested that magnet‑mediated hyperthermia at a higher temperature (50‑55˚C) can improve the abscopal antitumor effects and stimulate a greater endogenous immune response in carcinosarcoma‑bearing rats.

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1	van der Zee J: Heating the patient: a promising approach? Ann Oncol. 13:1173–1184. 2002.PubMed/NCBI
2	Hildebrandt B, Wust P, Ahlers O, et al: The cellular and molecular basis of hyperthermia. Crit Rev Oncol Hematol. 43:33–56. 2002. View Article : Google Scholar : PubMed/NCBI
3	Moroz P, Jones SK and Gray BN: Magnetically mediated hyperthermia: current status and future directions. Int J Hyperthermia. 18:267–284. 2002. View Article : Google Scholar : PubMed/NCBI
4	Wang H, Li X, Xi X, Hu B, Zhao L, Liao Y and Tang J: Effects of magnetic induction hyperthermia and radiotherapy alone or combined on a murine 4T1 metastatic breast cancer model. Intl J Hyperthermia. 27:563–572. 2011. View Article : Google Scholar : PubMed/NCBI
5	Camphausen K, Moses MA, Ménard C, et al: Radiation abscopal antitumor effect is mediated through p53. Cancer Res. 63:1990–1993. 2003.PubMed/NCBI
6	Blanquicett C, Saif MW, Buchsbaum DJ, et al: Antitumor efficacy of capecitabine and celecoxib in irradiated and lead-shielded, contralateral human BxPC-3 pancreatic cancer xenografts: clinical implications of abscopal effects. Clin Cancer Res. 11:8773–8781. 2005. View Article : Google Scholar
7	Sgouros G, Knox SJ, Joiner MC, Morgan WF and Kassis AI: MIRD continuing education: Bystander and low dose-rate effects: are these relevant to radionuclide therapy? J Nucl Med. 48:1683–1691. 2007. View Article : Google Scholar
8	Strauss AA, Appel M, Saphir O and Rabinovitz AJ: Immunologic resistance to carcinoma produced by electrocoagulation. Surg Gynecol Obstet. 121:989–996. 1965.PubMed/NCBI
9	Park BH, Koo BS, Kim YK and Kim MK: The induction of hyperthermia in rabbit liver by means of duplex stainless steel thermoseeds. Korean J Radiol. 3:98–104. 2002. View Article : Google Scholar
10	Tucker RD: Use of interstitial temperature self-regulating thermal rods in the treatment of prostate cancer. J Endourol. 17:601–607. 2003. View Article : Google Scholar : PubMed/NCBI
11	Izawa H, Hachiya Y, Kawai T, Muramatsu K, Narita Y, Ban N and Yoshizawa H: The effect of heat-treated human bone morphogenetic protein on clinical implantation. Clin Orthop Relat Res. 390:252–258. 2001. View Article : Google Scholar : PubMed/NCBI
12	Demaria S, Ng B, Devitt ML, Babb JS, Kawashima N, Liebes L and Formenti SC: Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediated. Int J Radiat Oncol Biol Phys. 58:862–870. 2004. View Article : Google Scholar
13	Van der Meeren A, Monti P, Vandamme M, Squiban C, Wysocki J and Griffiths N: Abdominal radiation exposure elicits inflammatory responses and abscopal effects in the lungs of mice. Radiat Res. 163:144–152. 2005.PubMed/NCBI
14	Srivastava PK and Maki RG: Stress-induced proteins in immune response to cancer. Curr Top Microbiol Immunol. 167:109–123. 1991.PubMed/NCBI
15	Wells AD, Rai SK, Salvato MS, Band H and Malkovsky M: Hsp72-mediated augmentation of MHC class I surface expression and endogenous antigen presentation. Int Immunol. 10:609–617. 1998. View Article : Google Scholar : PubMed/NCBI
16	Wells AD and Malkovsky M: Heat shock proteins, tumor immunogenicity and antigen presentation: an integrated view. Immunol Today. 21:129–132. 2000. View Article : Google Scholar : PubMed/NCBI
17	Ito A, Shinkai M, Honda H, Yoshikawa K, Saga S, Wakabayashi T, Yoshida J and Kobayashi T: Heat shock protein 70 expression induces antitumor immunity during intracellular hyperthermia using magnetite nanoparticles. Cancer Immunol Immunother. 52:80–88. 2003.
18	Todryk S, Melcher AA, Hardwick N, Linardakis E, Bateman A, Colombo MP, Stoppacciaro A and Vile RG: Heat shock protein 70 induced during tumor cell killing induces Th1 cytokines and targets immature dendritic cell precursors to enhance antigen uptake. J Immunol. 163:1398–1408. 1999.
19	Ito A, Shinkai M, Honda H, Wakabayashi T, Yoshida J and Kobayashi T: Augmentation of MHC class I antigen presentation via heat shock protein expression by hyperthermia. Cancer Immunol Immunother. 50:515–522. 2001. View Article : Google Scholar : PubMed/NCBI
20	Dressel R, Lübbers M, Walter L, Herr W and Günther E: Enhanced susceptibility to cytotoxic T lymphocytes without increase of MHC class I antigen expression after conditional overexpression of heat shock protein 70 in target cells. Eur J Immunol. 29:3925–3935. 1999. View Article : Google Scholar
21	Srivastava PK, Udono H, Blachere NE and Li Z: Heat shock proteins transfer peptides during antigen processing and CTL priming. Immunogenetics. 39:93–98. 1994. View Article : Google Scholar : PubMed/NCBI