Nitric Oxide Modulates Metabolic Processes in the Tumor Immune Microenvironment

McGinity, Christopher; Palmieri, Erika M.; Somasundaram, Veena; Bhattacharyya, Dibyangana; Ridnour, Lisa A.; Cheng, Robert; Ryan, Aideen E.; Glynn, Sharon A.; Thomas, Douglas D.; Miranda, Katrina M.; Anderson, Stephen; Lockett, Stephen; McVicar, Daniel W.; Wink, David A.

doi:10.3390/ijms22137068

Cited by 23 publications

(15 citation statements)

References 123 publications

(159 reference statements)

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“…This phenomenon also leads to hypoxia in the tumor microenvironment exacerbating the tumor immunosuppressive microenvironment. NO (nitric oxide), which regulates the normalization of tumor vasculature, can reverse immunosuppression by improving tumor hypoxia [ 82 – 84 ]. However, the available NO molecules and the donor suffer from poor stability.…”

Section: Cell Membrane Modified Nanomaterialsmentioning

confidence: 99%

Nanomaterials: small particles show huge possibilities for cancer immunotherapy

et al. 2022

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With the economy's globalization and the population's aging, cancer has become the leading cause of death in most countries. While imposing a considerable burden on society, the high morbidity and mortality rates have continuously prompted researchers to develop new oncology treatment options. Anti-tumor regimens have evolved from early single surgical treatment to combined (or not) chemoradiotherapy and then to the current stage of tumor immunotherapy. Tumor immunotherapy has undoubtedly pulled some patients back from the death. However, this strategy of activating or boosting the body's immune system hardly benefits most patients. It is limited by low bioavailability, low response rate and severe side effects. Thankfully, the rapid development of nanotechnology has broken through the bottleneck problem of anti-tumor immunotherapy. Multifunctional nanomaterials can not only kill tumors by combining anti-tumor drugs but also can be designed to enhance the body's immunity and thus achieve a multi-treatment effect. It is worth noting that the variety of nanomaterials, their modifiability, and the diversity of combinations allow them to shine in antitumor immunotherapy. In this paper, several nanobiotics commonly used in tumor immunotherapy at this stage are discussed, and they activate or enhance the body's immunity with their unique advantages. In conclusion, we reviewed recent advances in tumor immunotherapy based on nanomaterials, such as biological cell membrane modification, self-assembly, mesoporous, metal and hydrogels, to explore new directions and strategies for tumor immunotherapy.

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Section: Cell Membrane Modified Nanomaterialsmentioning

confidence: 99%

Nanomaterials: small particles show huge possibilities for cancer immunotherapy

et al. 2022

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“…Moreover, NO has been shown to counteract oxidative stress, inhibit cell death and facilitate pathogen scavenging [ 44 ]. Dysregulated metabolism of NO is central to the pathogenesis of many diseases, including, but not limited to: sepsis, cancers, hypertension, stroke, inflammation, diabetes and retinopathy [ 19 , 36 , 52 , 53 ].…”

Section: Gaseous Mediatorsmentioning

confidence: 99%

Gases in Sepsis: Novel Mediators and Therapeutic Targets

Zhu

Chambers

Zeng

et al. 2022

IJMS

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Sepsis, a potentially lethal condition resulting from failure to control the initial infection, is associated with a dysregulated host defense response to pathogens and their toxins. Sepsis remains a leading cause of morbidity, mortality and disability worldwide. The pathophysiology of sepsis is very complicated and is not yet fully understood. Worse still, the development of effective therapeutic agents is still an unmet need and a great challenge. Gases, including nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S), are small-molecule biological mediators that are endogenously produced, mainly by enzyme-catalyzed reactions. Accumulating evidence suggests that these gaseous mediators are widely involved in the pathophysiology of sepsis. Many sepsis-associated alterations, such as the elimination of invasive pathogens, the resolution of disorganized inflammation and the preservation of the function of multiple organs and systems, are shaped by them. Increasing attention has been paid to developing therapeutic approaches targeting these molecules for sepsis/septic shock, taking advantage of the multiple actions played by NO, CO and H2S. Several preliminary studies have identified promising therapeutic strategies for gaseous-mediator-based treatments for sepsis. In this review article, we summarize the state-of-the-art knowledge on the pathophysiology of sepsis; the metabolism and physiological function of NO, CO and H2S; the crosstalk among these gaseous mediators; and their crucial effects on the development and progression of sepsis. In addition, we also briefly discuss the prospect of developing therapeutic interventions targeting these gaseous mediators for sepsis.

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“…iNOS-derived NO is capable of producing cGMP and inducing posttranslational modifications (PTM) of proteins with thiol and amine groups ( 18–21 ). NO signaling is a function of NO concentration, and varied concentrations drive distinct signaling pathways ( 22 ). Within the TME, the influence of NO on protumor and antitumor functions is divided into three categories, depending on NO flux concentration: (i) cGMP-dependent signaling (<100 nmol/L NO), (ii) pro-oncogenic nitrosative signaling (50–300 nmol/L NO), and (iii) nitrosative stress signaling (500–2,000 nmol/L NO; Fig.…”

Section: Overview Of Nos Signalingmentioning

confidence: 99%

Targeting Nitric Oxide: Say NO to Metastasis

Reddy

Glynn

Billiar

et al. 2022

Clinical Cancer Research

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Utilizing targeted therapies capable of reducing cancer metastasis, targeting chemoresistant and self-renewing cancer stem cells, and augmenting the efficacy of systemic chemo/radiotherapies is vital to minimize cancer-associated mortality. Targeting nitric oxide synthase (NOS), a protein within the tumor microenvironment, has gained interest as a promising therapeutic strategy to reduce metastatic capacity and augment the efficacy of chemo/radiotherapies in various solid malignancies. Our review highlights the influence of nitric oxide (NO) in tumor progression and cancer metastasis, as well as promising preclinical studies that evaluated NOS inhibitors as anti-cancer therapies. Lastly, we highlight the prospects and outstanding challenges of using NOS inhibitors in the clinical setting.

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Nitric Oxide Modulates Metabolic Processes in the Tumor Immune Microenvironment

Cited by 23 publications

References 123 publications

Nanomaterials: small particles show huge possibilities for cancer immunotherapy

Nanomaterials: small particles show huge possibilities for cancer immunotherapy

Gases in Sepsis: Novel Mediators and Therapeutic Targets

Targeting Nitric Oxide: Say NO to Metastasis

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