Incomplete thermal ablation accelerates local and systemic tumor progression in an immunocompetent prostate cancer model.

Abstract

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 withtests of sublethal heat on Myc-CaP cell growth, followed bytumor growth studies on FVB mice ( = 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-testing cells demonstrated a substantial increase in luminescence over time, while the control group remained stable.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.