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

Abstract

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 tumorbearing 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.

Tumor vascular permeabilization using localized mild hyperthermia to improve macromolecule transport

“…In contrast, tumors exposed to thermal ablation showed significant cellular damage characterized by regions of thermonecrosis, corrupt extracellular matrix, damaged or enlarged cell nuclei, and coagulation (Figure 3F). These are some of the common observations in photothermal ablative therapies 40 . As further evidence that MHT caused no vascular hindrance by vascular damage and shutdown, dye flow was observed 24 h after treatment (Supplementary, Figure S3); unlike previous studies in which vascular occlusion was observed as early as 24 h after hyperthermia treatment 23 .…”

Stress-Induced, p53-Mediated Tumor Growth Inhibition of Melanoma by Modulated Electrohyperthermia in Mouse Models without Major Immunogenic Effects

“…The resulting tumor damage led to the release of the DAMP signaling molecules hsp70, HMGB1, and ATP. Although others reported that higher temperatures completely eradicated the primary melanoma tumors [30], it was also shown that although higher temperature (i.e., above 43 °C) was more effective in primary tumor destruction, it completely abrogated the resistance against secondary tumors, most probably by inducing necrotic cell death, which was not effective in mounting anti-tumor immunity [31]. Next, we dissected the molecular pathways leading to tumor regression induced by mEHT.…”

Combination of Bubble Liposomes and High-Intensity Focused Ultrasound (HIFU) Enhanced Antitumor Effect by Tumor Ablation

“…In addition, the tumor growth inhibition efficacy of the BLs and HIFU group was better than that of the HIFU alone group (p<0.05). It has been reported that local hightemperature hyperthermia (50-55°C) enhanced the indices of the T helper 1 (Th1) immune response, such as interleukin-2 (IL-2), interferon-gamma (IFN-γ), and tumor necrosis factoralpha (TNF-α) 8) ; therefore, it could be suggested that the antitumor effect of BLs and HIFU exposure was due to the ablation effect and immune response.…”