International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group · 2026
Incomplete thermal ablation accelerates local and systemic tumor progression in an immunocompetent prostate cancer model.
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Kader Avan, Ranner-Hafferl Marie-Luise Helene Hildegard, Polz Anna-Lena, Mülleder Michael, Farztdinov Vadim, Fendler Annika, Collettini Federico, Auer Timo Alexander
Аннотация
BACKGROUND: This study aims to evaluate the effects of sublethal hyperthermia on tumor growth of residual tumors in an immune-competent mouse model of prostate cancer.
MATERIALS AND METHODS: The study progressed through sequential experiments to assess the effects of incomplete thermal ablation, starting with in vitro tests of sublethal heat on Myc-CaP cell growth, followed by in vivo tumor growth studies on FVB mice (n = 84), proteomic analysis of residual tumors, immunohistochemical evaluation of markers of cellular and vascular proliferation as well as immune markers and Western blot analysis of cytokine and growth factor expression over time.
RESULTS: During in vitro-testing cells demonstrated a substantial increase in luminescence over time, while the control group remained stable. In vivo iTA led to significantly enhanced tumor growth both at the ablation site and in distant, untreated tumors, with increased cell proliferation, microvascular density, and expression of pro-tumorigenic factors (IL-6, HGF, VEGF). Proteomic analysis revealed that iTA induced strong early responses in wound healing, immune activation, and extracellular matrix remodeling, with systemic effects also seen in contralateral tumors. Immunohistochemistry and Western blot confirmed these findings and showed elevated immune cell infiltration, particularly CD45+ and CD11b + myeloid cells, indicating that iTA triggers a pro-inflammatory and pro-growth tumor microenvironment locally and systemically.
CONCLUSION: iTA can trigger tissue responses that accelerate tumor progression both locally and at distant sites, underscoring the need for careful pretreatment risk assessment (tumor size, achievable margins, proximity to critical structures) and vigilant monitoring of both treated and untreated disease after ablation.
MATERIALS AND METHODS: The study progressed through sequential experiments to assess the effects of incomplete thermal ablation, starting with in vitro tests of sublethal heat on Myc-CaP cell growth, followed by in vivo tumor growth studies on FVB mice (n = 84), proteomic analysis of residual tumors, immunohistochemical evaluation of markers of cellular and vascular proliferation as well as immune markers and Western blot analysis of cytokine and growth factor expression over time.
RESULTS: During in vitro-testing cells demonstrated a substantial increase in luminescence over time, while the control group remained stable. In vivo iTA led to significantly enhanced tumor growth both at the ablation site and in distant, untreated tumors, with increased cell proliferation, microvascular density, and expression of pro-tumorigenic factors (IL-6, HGF, VEGF). Proteomic analysis revealed that iTA induced strong early responses in wound healing, immune activation, and extracellular matrix remodeling, with systemic effects also seen in contralateral tumors. Immunohistochemistry and Western blot confirmed these findings and showed elevated immune cell infiltration, particularly CD45+ and CD11b + myeloid cells, indicating that iTA triggers a pro-inflammatory and pro-growth tumor microenvironment locally and systemically.
CONCLUSION: iTA can trigger tissue responses that accelerate tumor progression both locally and at distant sites, underscoring the need for careful pretreatment risk assessment (tumor size, achievable margins, proximity to critical structures) and vigilant monitoring of both treated and untreated disease after ablation.