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Forcing the Antitumor Effects of HSPs Using a Modulated Electric Field
Carrie Anne Minnaar1,2, Andras Szasz3
1Wits Donald Gordon Academic Hospital, Johannesburg 2193, South Africa.
Abstract:
The role of Heat Shock Proteins (HSPs) is a "double-edged sword" with regards to tumors. The location and interactions of HSPs determine their pro- or antitumor activity. The present review includes an overview of the relevant functions of HSPs, which could improve their antitumor activity. Promoting the antitumor processes could assist in the local and systemic management of cancer. We explore the possibility of achieving this by manipulating the electromagnetic interactions within the tumor microenvironment. An appropriate electric field may select and affect the cancer cells using the electric heterogeneity of the tumor tissue. This review describes the method proposed to effect such changes: amplitude-modulated radiofrequency (amRF) applied with a 13.56 MHz carrier frequency. We summarize the preclinical investigations of the amRF on the HSPs in malignant cells. The preclinical studies show the promotion of the expression of HSP70 on the plasma membrane, participating in the immunogenic cell death (ICD) pathway. The sequence of guided molecular changes triggers innate and adaptive immune reactions. The amRF promotes the secretion of HSP70 also in the extracellular matrix. The extracellular HSP70 accompanied by free HMGB1 and membrane-expressed calreticulin (CRT) form damage-associated molecular patterns encouraging the dendritic cells' maturing for antigen presentation. The process promotes CD8+ killer T-cells. Clinical results demonstrate the potential of this immune process to trigger a systemic effect. We conclude that the properly applied amRF promotes antitumor HSP activity, and in situ, it could support the tumor-specific immune effects produced locally but acting systemically for disseminated cells and metastatic lesions.
Insights
Amplitude-modulated radiofrequency (amRF) therapy enhances antitumor Heat Shock Protein (HSP) activity. This approach promotes immune responses against cancer cells, offering potential for systemic cancer treatment.
Area of Science:
- Oncology
- Immunology
- Biophysics
Background:
- Heat Shock Proteins (HSPs) exhibit dual roles in cancer, acting as either pro- or antitumor agents depending on their localization and interactions.
- Understanding HSP functions is crucial for developing strategies to enhance their antitumor capabilities for improved cancer management.
Purpose of the Study:
- To explore the manipulation of electromagnetic interactions within the tumor microenvironment to enhance antitumor HSP activity.
- To investigate the potential of amplitude-modulated radiofrequency (amRF) at 13.56 MHz to modulate HSPs for cancer therapy.
Main Methods:
- Review of preclinical investigations on the effects of amRF on HSPs in malignant cells.
- Analysis of amRF-induced changes in HSP70 expression and localization (plasma membrane and extracellular matrix).
- Examination of the formation of damage-associated molecular patterns (DAMPs) and subsequent immune cell activation.
Main Results:
- amRF treatment promotes the expression of HSP70 on the plasma membrane, facilitating immunogenic cell death (ICD).
- amRF enhances the secretion of extracellular HSP70, which, along with HMGB1 and calreticulin, forms DAMPs.
- These DAMPs promote dendritic cell maturation and antigen presentation, leading to enhanced CD8+ T-cell responses.
Conclusions:
- Properly applied amRF therapy can enhance antitumor HSP activity.
- This method shows potential for inducing localized, in situ, tumor-specific immune responses that act systemically to target disseminated cancer cells and metastatic lesions.
