Electrical Stimulation for Immune Modulation in Cancer Treatments

Immunotherapy is becoming a very common treatment for cancer, using approaches like checkpoint inhibition, T cell transfer therapy, monoclonal antibodies and cancer vaccination. However, these approaches involve high doses of immune therapeutics with problematic side effects. A promising approach to reducing the dose of immunotherapeutic agents given to a cancer patient is to combine it with electrical stimulation, which can act in two ways; it can either modulate the immune system to produce the immune cytokines and agents in the patient’s body or it can increase the cellular uptake of these immune agents via electroporation. Electrical stimulation in form of direct current has been shown to reduce tumor sizes in immune-competent mice while having no effect on tumor sizes in immune-deficient mice. Several studies have used nano-pulsed electrical stimulations to activate the immune system and drive it against tumor cells. This approach has been utilized for different types of cancers, like fibrosarcoma, hepatocellular carcinoma, human papillomavirus etc. Another common approach is to combine electrochemotherapy with immune modulation, either by inducing immunogenic cell death or injecting immunostimulants that increase the effectiveness of the treatments. Several therapies utilize electroporation to deliver immunostimulants (like genes encoded with cytokine producing sequences, cancer specific antigens or fragments of anti-tumor toxins) more effectively. Lastly, electrical stimulation of the vagus nerve can trigger production and activation of anti-tumor immune cells and immune reactions. Hence, the use of electrical stimulation to modulate the immune system in different ways can be a promising approach to treat cancer.

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The Interplay between Immunity and Microbiota at Intestinal Immunological Niche: The Case of Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms20030501 ◽

2019 ◽

Vol 20 (3) ◽

pp. 501 ◽

Cited By ~ 9

Author(s):

Rossella Cianci ◽

Laura Franza ◽

Giovanni Schinzari ◽

Ernesto Rossi ◽

Gianluca Ianiro ◽

...

Keyword(s):

Gene Expression ◽

Immune System ◽

Gut Microbiota ◽

Special Role ◽

Microbiota Composition ◽

Cancer Treatments ◽

Microbial Composition ◽

Different Types ◽

The Impact ◽

Influence Gene Expression

The gut microbiota is central to the pathogenesis of several inflammatory and autoimmune diseases. While multiple mechanisms are involved, the immune system clearly plays a special role. Indeed, the breakdown of the physiological balance in gut microbial composition leads to dysbiosis, which is then able to enhance inflammation and to influence gene expression. At the same time, there is an intense cross-talk between the microbiota and the immunological niche in the intestinal mucosa. These interactions may pave the way to the development, growth and spreading of cancer, especially in the gastro-intestinal system. Here, we review the changes in microbiota composition, how they relate to the immunological imbalance, influencing the onset of different types of cancer and the impact of these mechanisms on the efficacy of traditional and upcoming cancer treatments.

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Epidural Epinephrine and Clonidine

Anesthesiology ◽

10.1097/00000542-199710000-00011 ◽

1997 ◽

Vol 87 (4) ◽

pp. 785-794 ◽

Cited By ~ 70

Author(s):

Michele Curatolo ◽

Steen Petersen-Felix ◽

Lars Arendt-Nielsen ◽

Alex M. Zbinden

Keyword(s):

Electrical Stimulation ◽

Sural Nerve ◽

Temporal Summation ◽

Pain Tolerance ◽

Pain Rating ◽

Double Blind ◽

Pressure Pain ◽

Different Types ◽

Painful Area ◽

Stimulation Of

Background It is not known whether epidural epinephrine has an analgesic effect per se. The segmental distribution of clonidine epidural analgesia and its effects on temporal summation and different types of noxious stimuli are unknown. The aim of this study was to clarify these issues. Methods Fifteen healthy volunteers received epidurally (L2-L3 or L3-L4) 20 ml of either epinephrine, 100 microg, in saline; clonidine, 8 microg/kg, in saline; or saline, 0.9%, alone, on three different days in a randomized, double-blind, cross-over fashion. Pain rating after electrical stimulation, pinprick, and cold perception were recorded on the dermatomes S1, L4, L1, T9, T6, T1, and forehead. Pressure pain tolerance threshold was recorded at S1, T6, and ear. Pain thresholds to single and repeated (temporal summation) electrical stimulation of the sural nerve were determined. Results Epinephrine significantly reduced sensitivity to pinprick at L1-L4-S1. Clonidine significantly decreased pain rating after electrical stimulation at L1-L4 and sensitivity to pinprick and cold at L1-L4-S1, increased pressure pain tolerance threshold at S1, and increased thresholds after single and repeated stimulation of the sural nerve. Conclusions Epidural epinephrine and clonidine produce segmental hypoalgesia. Clonidine bolus should be administered at a spinal level corresponding to the painful area. Clonidine inhibits temporal summation elicited by repeated electrical stimulation and may therefore attenuate spinal cord hyperexcitability.

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Stimulation of an immune system by different types of allergens causes seasonal (late spring and summer) factors to increase probability of allergic rhinitis symptoms. The Epidemiology of Allergic Diseases in Poland (ECAP) survey: part two

Advances in Dermatology and Allergology ◽

10.5114/ada.2021.107925 ◽

2021 ◽

Vol 38 (3) ◽

pp. 384-388

Author(s):

Andrzej Namysłowski ◽

Agnieszka Lipiec ◽

Wojciech Zieliński ◽

Filip Raciborski ◽

Aneta Tomaszewska ◽

...

Keyword(s):

Allergic Rhinitis ◽

Immune System ◽

Allergic Diseases ◽

Late Spring ◽

Different Types ◽

Stimulation Of

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Sound Production in a Brazilian Cicada

Journal of Experimental Biology ◽

10.1242/jeb.51.2.325 ◽

1969 ◽

Vol 51 (2) ◽

pp. 325-337

Author(s):

D. J. AIDLEY

Keyword(s):

Electrical Stimulation ◽

Physical Properties ◽

Sound Production ◽

Natural Habitat ◽

Sound Field ◽

Sound Intensity ◽

Different Types ◽

Stimulation Of

1. Some aspects of the physiology of sound production in the Brazilian cicada Fidicana rana Walker have been investigated. 2. Three types of natural song are described. Singing can also be induced by electrical stimulation of the head. 3. The tymbal muscles are neurogenically activated and contract alternately. 4. The directional properties of the sound field produced by clicking of the tymbal are described, and the physical properties of the system necessary to produce this directionality are discussed. 5. Removal of the abdomen does not decrease the sound intensity during song produced by electrical stimulation, hence it is concluded that the abdominal air sac does not act as a resonant chamber. 6. The means whereby the sound intensity is varied are discussed. 7. A brief account is given of the occurrence of the different types of song in the natural habitat.

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The Roles of Alternative Splicing in Tumor-immune Cell Interactions

Current Cancer Drug Targets ◽

10.2174/1568009620666200619123725 ◽

2020 ◽

Vol 20 (10) ◽

pp. 729-740

Author(s):

Yue Wang ◽

Honglei Zhang ◽

Baowei Jiao ◽

Jianyun Nie ◽

Xiyin Li ◽

...

Keyword(s):

Immune System ◽

Alternative Splicing ◽

Immune Responses ◽

Immune Cell ◽

Hallmarks Of Cancer ◽

Adaptive Immune Responses ◽

Adaptive Immune ◽

Hematological Cancers ◽

Different Types ◽

Specific Antigens

Alternative splicing (AS) plays a significant role in the hallmarks of cancer and can provide neoantigens for immunotherapy. Here, we summarize recent advances in immune system associated tumor specific-antigens (TSAs) produced by AS. We further discuss the regulating mechanisms involved in AS-mediated innate and adaptive immune responses and the anti-tumoral and protumoral roles in different types of cancer. For example, ULBP1_RI, MLL5Δ21spe, NKp44-1Δ5, MHC-IΔ7, CD200SΔ1, 2, PVR α/β/γ/δ and IL-33 variants 1/2/3 act as regulators in solid tumors and IPAK4-L and, FOXP1ΔN100 exhibit functions in hematological cancers.

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Vaccination with Recombinant N-Terminal Domain of Als1p Improves Survival during Murine Disseminated Candidiasis by Enhancing Cell-Mediated, Not Humoral, Immunity

Infection and Immunity ◽

10.1128/iai.73.2.999-1005.2005 ◽

2005 ◽

Vol 73 (2) ◽

pp. 999-1005 ◽

Cited By ~ 58

Author(s):

Ashraf S. Ibrahim ◽

Brad J. Spellberg ◽

Valentina Avenissian ◽

Yue Fu ◽

Scott G. Filler ◽

...

Keyword(s):

Humoral Immunity ◽

Immune Modulation ◽

Passive Immunization ◽

Bloodstream Infections ◽

Delayed Type Hypersensitivity ◽

Disseminated Candidiasis ◽

Terminal Domain ◽

Deficient Mice ◽

Stimulation Of

ABSTRACT Candida spp. are opportunistic fungal pathogens that are among the most common causes of nosocomial bloodstream infections. The mortality attributable to disseminated candidiasis is 40 to 50% despite antifungal therapy. Clearly, new strategies are needed to prevent this life-threatening infection. Because risk factors for disseminated candidiasis are well defined and frequently of limited duration, vaccination is an appealing prophylactic strategy. We have identified a cell surface protein, Als1p, that mediates adherence of Candida albicans to a variety of human substrates and plastic. Here we report that immunizing BALB/c mice with the recombinant N-terminal domain of Als1p (rAls1p-N) improved survival during a subsequent challenge with a lethal inoculum of C. albicans. The protective 20-μg dose of rAls1p-N significantly increased Candida stimulation of Th1 splenocytes and increased in vivo delayed-type hypersensitivity. In contrast, antibody titers did not correlate with protection. Finally, the vaccine was not protective in T-cell-deficient mice but was protective in B-cell-deficient mice. These data indicate that the mechanism of action of the rAls1p-N vaccine is stimulation of cell-mediated, rather than humoral, immunity against C. albicans. The majority of efforts to date have focused on the development of passive immunization strategies to prevent or treat disseminated candidiasis. In contrast, our results provide proof of principle for vaccination with an adhesin of C. albicans and emphasize the potential for cell-mediated immune modulation as a prophylactic or therapeutic strategy against disseminated candidiasis.

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Orbitofrontal cortex contributes to the comparison of values underlying economic choices

10.1101/2021.12.16.473020 ◽

2021 ◽

Author(s):

Sebastien Ballesta ◽

Weikang Shi ◽

Camillo Padoa-Schioppa

Keyword(s):

Electrical Stimulation ◽

Recent Work ◽

Neuronal Activity ◽

Orbitofrontal Cortex ◽

Decision Process ◽

Neuronal Populations ◽

Different Types ◽

Economic Choices ◽

Stimulation Of

Economic choices between goods entail the computation and comparison of subjective values. Previous studies examined neuronal activity in the orbitofrontal cortex (OFC) of monkeys choosing between different types of juices. Three groups of neurons were identified: offer value cells encoding the value of individual offers, chosen juice cells encoding the identity of the chosen juice, and chosen value cells encoding the value of the chosen offer. The encoded variables capture both the input (offer value) and the output (chosen juice, chosen value) of the decision process, suggesting that values are compared within OFC. Recent work demonstrates that choices are causally linked to the activity of offer value cells. Conversely, the hypothesis that OFC contributes to value comparison has not been confirmed. Here we show that weak electrical stimulation of OFC specifically disrupts value comparison without altering offer values. This result implies that neuronal populations in OFC participate in the decision process.

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