Antitumor effect and immune response induced by local hyperthermia in B16 murine melanoma: Effect of thermal dose

Li,Dan  Ye; Tang,Yang  Ping; Zhao,Ling   Yun; Geng,Chuan   Ying; Tang,Jin   Tian

doi:10.3892/ol.2012.804

Antitumor effect and immune response induced by local hyperthermia in B16 murine melanoma: Effect of thermal dose

Authors:
- Dan Ye Li
- Yang Ping Tang
- Ling Yun Zhao
- Chuan Ying Geng
- Jin Tian Tang
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Affiliations: Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China, Key Laboratory of Particle and Radiation Imaging, Ministry of Education, Department of Engineering Physics, Tsinghua University, Beijing 100084, P.R. China, China-Japan Friendship Hospital, Beijing 100029, P.R. China
Published online on: July 16, 2012 https://doi.org/10.3892/ol.2012.804
Pages: 711-718

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Abstract

This study aimed at investigating the antitumor effect and immune response induced by local high-temperature hyperthermia at different thermal doses in B16 murine melanoma. The screened optimal thermal dose (50˚C, 15 min) which was demonstrated to be the most effective in immune response activation was applied to the treatment of lung metastasis. The optimal thermal dose was determined by evaluating the tumor volume change, survival period of tumor-bearing mice, and immune indices including interleukin (IL)-2, interferon (IFN)-γ and TNF-α mRNA expression in the spleen of mice subjected to local hyperthermia at various thermal doses. The activation of the immune response was further investigated by rechallenging the cured mice 60 days after hyperthermia treatment. The screened optimal thermal dose combined with immunoadjuvant compound 48/80 was applied for melanoma lung metastasis. While local hyperthermia effectively inhibited B16 melanoma tumor growth and prolonged the survival period of tumor-bearing mice, the antitumor immunity was significantly enhanced and the effect was thermal dose‑dependent. Higher temperatures (≥50˚C) induced a significant effect even with a short treatment time (≤15 min). No tumor regrowth was observed for rechallenged B16 melanoma in mice following treatment with local hyperthermia at a higher temperature. Local hyperthermia by optimal thermal dose in combination with immunoadjuvant compound 48/80 is an effective approach for the treatment of B16 melanoma lung metastasis. This study indicated that the use of a local high‑temperature hyperthermia protocol inhibits tumor growth and stimulates a favorable antitumor immune response against malignant melanoma. The results of these experiments may have clinical significance for the treatment of melanoma.

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