Immunogenic Effect of Hyperthermia on Enhancing Radiotherapeutic Efficacy

Lee, Sung-Min; Son, Bong Soo; Park, Gaeul; Kim, Hyun Woo; Kang, Hyunkoo; Jeon, Jaewan; Youn, HyeSook; Youn, BuHyun

doi:10.3390/ijms19092795

Cited by 42 publications

(51 citation statements)

References 193 publications

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“…Finally, based on the increased number of F4/80+CD11b+ macrophages, we suggest that this cell population has also an important role in the anti-tumor effect of mEHT. Specifically, the p53-, p21-, and p27-expressing apoptotic/senescent cells in the treated tumors can be cleared away by macrophages [48], whose phagocytic/clearance function is also known to be enhanced by hyperthermia [49].…”

Section: Discussionmentioning

confidence: 99%

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

Besztercei

Vancsik

Benedek

et al. 2019

IJMS

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Modulated electrohyperthermia (mEHT), an innovative complementary technique of radio-, chemo-, and targeted oncotherapy modalities, can induce tumor apoptosis and contribute to a secondary immune-mediated cancer death. Here, we tested the efficiency of high-fever range (~42 °C) mEHT on B16F10 melanoma both in cell culture and allograft models. In vivo, mEHT treatment resulted in significant tumor size reduction when repeated three times, and induced major stress response as indicated by upregulated cytoplasmic and cell membrane hsp70 levels. Despite the increased PUMA and apoptosis-inducing factor 1, and moderate rise in activated-caspase-3, apoptosis was not significant. However, phospho-H2AX indicated DNA double-strand breaks, which upregulated p53 protein and its downstream cyclin-dependent kinase inhibitors p21waf1 and p27kip. Combined in vitro treatment with mEHT and the p53 activator nutlin-3a additively reduced cell viability compared to monotherapies. Though mEHT promoted the release of damage-associated molecular pattern (DAMP) damage signaling molecules hsp70, HMGB1 and ATP to potentiate the tumor immunogenicity of melanoma allografts, it reduced MHC-I and melan-A levels in tumor cells. This might explain why the number of cytotoxic T cells was moderately reduced, while the amount of natural killer (NK) cells was mainly unchanged and only macrophages increased significantly. Our results suggest that mEHT-treatment-related tumor growth control was primarily mediated by cell-stress-induced p53, which upregulated cyclin-dependent kinase inhibitors. The downregulated tumor antigen-presenting machinery may explain the reduced cytotoxic T-cell response despite increased DAMP signaling. Decreased tumor antigen and MHC-I levels suggest that natural killer (NK) cells and macrophages were the major contributors to tumor eradication.

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Section: Discussionmentioning

confidence: 99%

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

Besztercei

Vancsik

Benedek

et al. 2019

IJMS

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“…HT elicits innate and adaptive immune responses which may enhance its treatment effects [3,42,43]. Studies have found that HT may increase the cytotoxic activity of natural killer (NK) and CD8þ T cells against tumor cells [44,45].…”

Section: Ht and Immunomodulationmentioning

confidence: 99%

Hyperthermia treatment advances for brain tumors

Skandalakis

Rivera

Rizea

et al. 2020

International Journal of Hyperthermia

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Hyperthermia therapy (HT) of cancer is a well-known treatment approach. With the advent of new technologies, HT approaches are now important for the treatment of brain tumors. We review current clinical applications of HT in neuro-oncology and ongoing preclinical research aiming to advance HT approaches to clinical practice. Laser interstitial thermal therapy (LITT) is currently the most widely utilized thermal ablation approach in clinical practice mainly for the treatment of recurrent or deepseated tumors in the brain. Magnetic hyperthermia therapy (MHT), which relies on the use of magnetic nanoparticles (MNPs) and alternating magnetic fields (AMFs), is a new quite promising HT treatment approach for brain tumors. Initial MHT clinical studies in combination with fractionated radiation therapy (RT) in patients have been completed in Europe with encouraging results. Another combination treatment with HT that warrants further investigation is immunotherapy. HT approaches for brain tumors will continue to a play an important role in neuro-oncology.

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“…These, on the one hand result in greater drug delivery to tumor and cells, and on the other hand increase the sensitivity of cells to chemotherapeutics and radiation, boosting the effect of chemotherapy and radiotherapy when combined with hyperthermia [ 71 , 72 ]. In addition, mild hyperthermia can induce or improve antitumor activity [ 73 , 74 , 75 , 76 ]. For example, many of the heat-shock proteins (HSPs) released from heat-stressed cancer cells can activate antigen-presenting cells (APCs) [ 77 , 78 , 79 ].…”

Section: Hyperthermia and Its Clinical Applicationmentioning

confidence: 99%

Hyperthermia and Temperature-Sensitive Nanomaterials for Spatiotemporal Drug Delivery to Solid Tumors

Amin¹,

Huang²,

Seynhaeve³

et al. 2020

Pharmaceutics

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Nanotechnology has great capability in formulation, reduction of side effects, and enhancing pharmacokinetics of chemotherapeutics by designing stable or long circulating nano-carriers. However, effective drug delivery at the cellular level by means of such carriers is still unsatisfactory. One promising approach is using spatiotemporal drug release by means of nanoparticles with the capacity for content release triggered by internal or external stimuli. Among different stimuli, interests for application of external heat, hyperthermia, is growing. Advanced technology, ease of application and most importantly high level of control over applied heat, and as a result triggered release, and the adjuvant effect of hyperthermia in enhancing therapeutic response of chemotherapeutics, i.e., thermochemotherapy, make hyperthermia a great stimulus for triggered drug release. Therefore, a variety of temperature sensitive nano-carriers, lipid or/and polymeric based, have been fabricated and studied. Importantly, in order to achieve an efficient therapeutic outcome, and taking the advantages of thermochemotherapy into consideration, release characteristics from nano-carriers should fit with applicable clinical thermal setting. Here we introduce and discuss the application of the three most studied temperature sensitive nanoparticles with emphasis on release behavior and its importance regarding applicability and therapeutic potentials.

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Immunogenic Effect of Hyperthermia on Enhancing Radiotherapeutic Efficacy

Cited by 42 publications

References 193 publications

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

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

Hyperthermia treatment advances for brain tumors

Hyperthermia and Temperature-Sensitive Nanomaterials for Spatiotemporal Drug Delivery to Solid Tumors

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