Potential of Magnetic Hyperthermia to Stimulate Localized Immune Activation

TLDR

Magnetic hyperthermia (MH) uses the heat‑releasing properties of superparamagnetic iron oxide nanoparticles (SPIONs) to potentially stimulate immune activation within the tumor microenvironment while sparing normal tissues. The study aims to assess the feasibility of localized MH in vivo. The authors injected SPIONs intratumorally, tracked their distribution with Zirconium‑89 PET, histology, and electron microscopy, applied an alternating magnetic field to generate in‑situ heating monitored by thermal imaging, and used flow cytometry to profile immune cells from tumors and draining lymph nodes. The treatment retained an average of 49 % of SPIONs in the tumor, induced localized heat‑shock protein expression, inhibited tumor growth, and elicited an anti‑tumor immune response characterized by increased activated cytotoxic T cells, proliferating regulatory T cells, and complementary changes in draining lymph nodes.

Abstract

Abstract Magnetic hyperthermia (MH) harnesses the heat‐releasing properties of superparamagnetic iron oxide nanoparticles (SPIONs) and has potential to stimulate immune activation in the tumor microenvironment whilst sparing surrounding normal tissues. To assess feasibility of localized MH in vivo, SPIONs are injected intratumorally and their fate tracked by Zirconium‐89‐positron emission tomography, histological analysis, and electron microscopy. Experiments show that an average of 49% (21–87%, n = 9) of SPIONs are retained within the tumor or immediately surrounding tissue. In situ heating is subsequently generated by exposure to an externally applied alternating magnetic field and monitored by thermal imaging. Tissue response to hyperthermia, measured by immunohistochemical image analysis, reveals specific and localized heat‐shock protein expression following treatment. Tumor growth inhibition is also observed. To evaluate the potential effects of MH on the immune landscape, flow cytometry is used to characterize immune cells from excised tumors and draining lymph nodes. Results show an influx of activated cytotoxic T cells, alongside an increase in proliferating regulatory T cells, following treatment. Complementary changes are found in draining lymph nodes. In conclusion, results indicate that biologically reactive MH is achievable in vivo and can generate localized changes consistent with an anti‐tumor immune response.