The Effects of Localized Heat on the Hallmarks of Cancer

Hannon, Gary; Tansi, Felista L.; Hilger, Ingrid; Prina-Mello, Adriele

doi:10.1002/adtp.202000267

Cited by 42 publications

(32 citation statements)

References 292 publications

(357 reference statements)

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“…This process may involve the activation of TRPV1 in the TME. Conventional methods for applying mild heat heavily rely on external heat sources, including near-infrared light coupled with photosensitizers, ultrasonic systems, and microwave. ,,, Nevertheless, these methods encounter limitations, particularly in achieving uniform heating across entire tumor volumes due to their restricted tumor penetration and the requirement for precise knowledge of tumor positioning prior to applying heat sources. , Furthermore, maintaining accurate temperature regulation within the narrow range of 43–45 °C poses challenges, heightening the potential risk of harming surrounding healthy tissues, such as inducing skin burns. , …”

Section: Resultsmentioning

confidence: 99%

“…53,54 Furthermore, maintaining accurate temperature regulation within the narrow range of 43−45 °C poses challenges, heightening the potential risk of harming surrounding healthy tissues, such as inducing skin burns. 53,54 In response to the aforementioned limitations of physical stimulation with mild heat, this study suggests employing capsaicin for chemical stimulation to activate TRPV1 in the TME. This strategy is accomplished by an intelligent immunomodulatory mechanism facilitated by the BMS202-Figures 7a) and increased T cell recruitment into the TME (Figures 7a,b).…”

Section: Synthesis and Characterization Of Capsaicin Prodrugmentioning

confidence: 99%

“…8,23,51,52 Nevertheless, these methods encounter limitations, particularly in achieving uniform heating across entire tumor volumes due to their restricted tumor penetration and the requirement for precise knowledge of tumor positioning prior to applying heat sources. 53,54 Furthermore, maintaining accurate temperature regulation within the narrow range of 43−45 °C poses challenges, heightening the potential risk of harming surrounding healthy tissues, such as inducing skin burns. 53,54 In response to the aforementioned limitations of physical stimulation with mild heat, this study suggests employing capsaicin for chemical stimulation to activate TRPV1 in the TME.…”

Section: Synthesis and Characterization Of Capsaicin Prodrugmentioning

confidence: 99%

See 2 more Smart Citations

Immunomodulatory Prodrug Micelles Imitate Mild Heat Effects to Reshape Tumor Microenvironment for Enhanced Cancer Immunotherapy

Ngo,

Wang,

Pan

et al. 2024

ACS Nano

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Physical stimulation with mild heat possesses the notable ability to induce immunomodulation within the tumor microenvironment (TME). It transforms the immunosuppressive TME into an immune-active state, making tumors more receptive to immune checkpoint inhibitor (ICI) therapy. Transient receptor potential vanilloid 1 (TRPV1), which can be activated by mild heat, holds the potential to induce these alterations in the TME. However, achieving precise temperature control within tumors while protecting neighboring tissues remains a significant challenge when using external heat sources. Taking inspiration from the heat sensation elicited by capsaicin-containing products activating TRPV1, this study employs capsaicin to chemically stimulate TRPV1, imitating immunomodulatory benefits akin to those induced by mild heat. This involves developing a glutathione (GSH)-responsive immunomodulatory prodrug micelle system to deliver capsaicin and an ICI (BMS202) concurrently. Following intravenous administration, the prodrug micelles accumulate at the tumor site through the enhanced permeability and retention effect. Within the GSH-rich TME, the micelles disintegrate and release capsaicin and BMS202. The released capsaicin activates TRPV1 expressed in the TME, enhancing programmed death ligand 1 expression on tumor cell surfaces and promoting T cell recruitment into the TME, rendering it more immunologically active. Meanwhile, the liberated BMS202 blocks immune checkpoints on tumor cells and T cells, activating the recruited T cells and ultimately eradicating the tumors. This innovative strategy represents a comprehensive approach to fine-tune the TME, significantly amplifying the effectiveness of cancer immunotherapy by exploiting the TRPV1 pathway and enabling in situ control of immunomodulation within the TME.

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Section: Resultsmentioning

confidence: 99%

Section: Synthesis and Characterization Of Capsaicin Prodrugmentioning

confidence: 99%

Section: Synthesis and Characterization Of Capsaicin Prodrugmentioning

confidence: 99%

See 1 more Smart Citation

Immunomodulatory Prodrug Micelles Imitate Mild Heat Effects to Reshape Tumor Microenvironment for Enhanced Cancer Immunotherapy

Ngo,

Wang,

Pan

et al. 2024

ACS Nano

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“…Leonard Taylor, the inventor of the microwave scalpel, described the potential utilization of microwaves in the treatment of various types of solid tumors as a tool for microwave surgery [498]. The technology has since evolved, to include microwave treatments of several types of cancer, including cancers of the liver, kidney, breast, and lungs, just to mention a few [499].…”

Section: A Ablation and Catheter Ablationmentioning

confidence: 99%

Applications of Microwaves in Medicine

Chiao

Lin

et al. 2023

IEEE J. Microw.

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Advances and updates in medical applications utilizing microwave techniques and technologies are reviewed in this paper. The article aims to provide an overview of enablers for microwave medical applications and their recent progress. The emphasis focuses on the applications of microwaves, in the following order, for 1) signal and data communication for implants and wearables through the human body, 2) electromagnetic energy transfer through tissues, 3) noninvasive, remote or in situ physical and biochemical sensing, and 4) therapeutic purposes by changing tissue properties with controlled thermal effects. For signal and data communication and wireless power transfer, implant and wearable applications are discussed in the categories of pacemakers, endoscopic capsules, brain interfaces, intraocular, cardiac and intracranial pressure sensors, neurostimulators, endoluminal implants, artificial retina, smart lenses, and cochlear implants. For noninvasive sensing, remote vital sign radar, biological cell probing, magnetic resonance and microwave imaging, biochemical, blood glucose, hydration and biomarker sensing applications are introduced. For therapeutic uses, the developments of microwave ablation, balloon angioplasty, and hyperthermia applications are reviewed. The scopes of this article mainly concentrate on the research and development efforts in the past 20 years. Recent review articles on specific topics are cited with accomplishment highlights and trends deliberated. At the end of this article, a brief history of the IEEE Microwave Theory and Techniques Society (MTT-S) Biological Effects and Medical Applications committee and the contributions by its members to the promotion and advancement of microwave technologies in medical fields are chronicled.

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“…We have adopted this classification because temperatures >44 °C can increase tumor hypoxia in canine soft tissue sarcomas, whereas below this threshold, hypoxia is either not affected or is reduced [ 62 , 63 ]. Others have used adjectival descriptors of mild (40–42 °C), moderate (42–45 °C) and T > 45 °C as causing irreversible damage [ 64 ]. This classification is similar to what we describe.…”

Section: Introductionmentioning

confidence: 99%

Accurate Three-Dimensional Thermal Dosimetry and Assessment of Physiologic Response Are Essential for Optimizing Thermoradiotherapy

Dewhirst

Oleson

Kirkpatrick

et al. 2022

Cancers

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Numerous randomized trials have revealed that hyperthermia (HT) + radiotherapy or chemotherapy improves local tumor control, progression free and overall survival vs. radiotherapy or chemotherapy alone. Despite these successes, however, some individuals fail combination therapy; not every patient will obtain maximal benefit from HT. There are many potential reasons for failure. In this paper, we focus on how HT influences tumor hypoxia, since hypoxia negatively influences radiotherapy and chemotherapy response as well as immune surveillance. Pre-clinically, it is well established that reoxygenation of tumors in response to HT is related to the time and temperature of exposure. In most pre-clinical studies, reoxygenation occurs only during or shortly after a HT treatment. If this were the case clinically, then it would be challenging to take advantage of HT induced reoxygenation. An important question, therefore, is whether HT induced reoxygenation occurs in the clinic that is of radiobiological significance. In this review, we will discuss the influence of thermal history on reoxygenation in both human and canine cancers treated with thermoradiotherapy. Results of several clinical series show that reoxygenation is observed and persists for 24–48 h after HT. Further, reoxygenation is associated with treatment outcome in thermoradiotherapy trials as assessed by: (1) a doubling of pathologic complete response (pCR) in human soft tissue sarcomas, (2) a 14 mmHg increase in pO2 of locally advanced breast cancers achieving a clinical response vs. a 9 mmHg decrease in pO2 of locally advanced breast cancers that did not respond and (3) a significant correlation between extent of reoxygenation (as assessed by pO2 probes and hypoxia marker drug immunohistochemistry) and duration of local tumor control in canine soft tissue sarcomas. The persistence of reoxygenation out to 24–48 h post HT is distinctly different from most reported rodent studies. In these clinical series, comparison of thermal data with physiologic response shows that within the same tumor, temperatures at the higher end of the temperature distribution likely kill cells, resulting in reduced oxygen consumption rate, while lower temperatures in the same tumor improve perfusion. However, reoxygenation does not occur in all subjects, leading to significant uncertainty about the thermal–physiologic relationship. This uncertainty stems from limited knowledge about the spatiotemporal characteristics of temperature and physiologic response. We conclude with recommendations for future research with emphasis on retrieving co-registered thermal and physiologic data before and after HT in order to begin to unravel complex thermophysiologic interactions that appear to occur with thermoradiotherapy.

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The Effects of Localized Heat on the Hallmarks of Cancer

Cited by 42 publications

References 292 publications

Immunomodulatory Prodrug Micelles Imitate Mild Heat Effects to Reshape Tumor Microenvironment for Enhanced Cancer Immunotherapy

Immunomodulatory Prodrug Micelles Imitate Mild Heat Effects to Reshape Tumor Microenvironment for Enhanced Cancer Immunotherapy

Applications of Microwaves in Medicine

Accurate Three-Dimensional Thermal Dosimetry and Assessment of Physiologic Response Are Essential for Optimizing Thermoradiotherapy

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