Persano, S.; Vicini, F.; Poggi, A.; Fernandez, J.L.C.; Rizzo, G.M.R.; Gavilán, H.; Silvestri, N.; Pellegrino, T. Elucidating the Innate Immunological Effects of Mild Magnetic Hyperthermia on U87 Human Glioblastoma Cells: An In Vitro Study. Pharmaceutics2021, 13, 1668.
Persano, S.; Vicini, F.; Poggi, A.; Fernandez, J.L.C.; Rizzo, G.M.R.; Gavilán, H.; Silvestri, N.; Pellegrino, T. Elucidating the Innate Immunological Effects of Mild Magnetic Hyperthermia on U87 Human Glioblastoma Cells: An In Vitro Study. Pharmaceutics 2021, 13, 1668.
Persano, S.; Vicini, F.; Poggi, A.; Fernandez, J.L.C.; Rizzo, G.M.R.; Gavilán, H.; Silvestri, N.; Pellegrino, T. Elucidating the Innate Immunological Effects of Mild Magnetic Hyperthermia on U87 Human Glioblastoma Cells: An In Vitro Study. Pharmaceutics2021, 13, 1668.
Persano, S.; Vicini, F.; Poggi, A.; Fernandez, J.L.C.; Rizzo, G.M.R.; Gavilán, H.; Silvestri, N.; Pellegrino, T. Elucidating the Innate Immunological Effects of Mild Magnetic Hyperthermia on U87 Human Glioblastoma Cells: An In Vitro Study. Pharmaceutics 2021, 13, 1668.
Abstract
Cancer immunotherapies are gaining a large popularity and many of them have been approved as standard second-line or in some cases even as first-line treatment for a wide range of cancers. However, immunotherapy has not shown a clinically relevant success in glioblastoma (GBM), principally due to the brain’s “immune-privileged” status and the peculiar tumor microenvironment (TME) of GBM featured by lack of presence of tumor-infiltrating lymphocytes and the establishment of immunosuppressive mechanisms. Emerging evidence has highlighted the key role played by innate immune cells in immunosurveillance and in initiating and driving immune responses against GBM. Immunogenic cell death (ICD) is a promising approach to elicit direct activation of the innate immune system by inducing in target cancer cells the expression of molecular signatures recognized through a repertoire of innate immune cell pattern recognition receptors (PRRs) by effector innate immune cells. Herein, we explored local mild thermal treatment, generated by using ultrasmall (size ~ 17 nm) cubic-shaped iron oxide nanoparticles exposed to an external alternating magnetic field (AMF), to induce ICD in U87 glioblastoma cells. In accordance with what has been previously observed with other types of tumors, we found that mild hyperthermia modulates the immunological profile of U87 glioblastoma cells by inducing stress-associated signals leading to enhanced phagocytosis and killing of U87 cells by macrophages. Finally, we demonstrated that mild magnetic hyperthermia has a modulatory effect on the expression of inhibitory and activating NK cell ligands on target cells. Interestingly, alteration in the expression of NK ligands, caused by mild hyperthermia treatment, in U87 glioblastoma cells, increased their susceptibility to NK cell killing and NK cell functionality. The overall findings demonstrate that mild magnetic hyperthermia stimulates ICD and sensitizes GBM cells to NK-mediated killing by inducing the upregulation of specific stress ligands, providing a novel immunotherapeutic approach for GBM treatment, with potential to synergize with existing NK cell-based therapies thus improving their therapeutic outcomes.
Biology and Life Sciences, Immunology and Microbiology
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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