Cancer Salt Nostalgia

Allu, Aashish S.; Tiriveedhi, Venkataswarup

doi:10.3390/cells10061285

Cited by 9 publications

(9 citation statements)

References 89 publications

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“…The impact of ICI on metabolic diseases need to be studied in future. All pre-clinical tumor inoculation models (including our current study) have a generic problem of studying tumor responses during an acute immune activation phase [ 28 ]. However, human cancers are a consequence of initial immune elimination followed by cancer growth during the immune exhaustion phase.…”

Section: Discussionmentioning

confidence: 99%

“…However, HS diet is also associated with the exacerbation of cardiovascular, autoimmune, and other chronic inflammatory diseases [ 27 ]. The impacts of an HS diet on the anti-cancer efficiency and off-target effects of ICI are not well understood [ 28 , 29 ]. The tonicity sensitive transcription factor, TonEBP, also called nuclear factor of activated T-cells 5 (NFAT5), is known to play a critical role in osmotic stress-mediated inflammatory responses in lymph nodes and spleen, leading to immune cell differentiation, activation and proliferation [ 30 , 31 , 32 ].…”

Section: Introductionmentioning

confidence: 99%

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Low-Salt Diet Reduces Anti-CTLA4 Mediated Systemic Immune-Related Adverse Events while Retaining Therapeutic Efficacy against Breast Cancer

Khandekar

Dahunsi

Esteve

et al. 2022

Biology

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Immune checkpoint inhibitor (ICI) therapy has revolutionized the breast cancer treatment landscape. However, ICI-induced systemic inflammatory immune-related adverse events (irAE) remain a major clinical challenge. Previous studies in our laboratory and others have demonstrated that a high-salt (HS) diet induces inflammatory activation of CD4+T cells leading to anti-tumor responses. In our current communication, we analyzed the impact of dietary salt modification on therapeutic and systemic outcomes in breast-tumor-bearing mice following anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) monoclonal antibody (mAb) based ICI therapy. As HS diet and anti-CTLA4 mAb both exert pro-inflammatory activation of CD4+T cells, we hypothesized that a combination of these would lead to enhanced irAE response, while low-salt (LS) diet through blunting peripheral inflammatory action of CD4+T cells would reduce irAE response. We utilized an orthotopic murine breast tumor model by injecting Py230 murine breast cancer cells into syngeneic C57Bl/6 mice. In an LS diet cohort, anti-CTLA4 mAb treatment significantly reduced tumor progression (day 35, 339 ± 121 mm3), as compared to isotype mAb (639 ± 163 mm3, p < 0.05). In an HS diet cohort, treatment with anti-CTLA4 reduced the survival rate (day 80, 2/15) compared to respective normal/regular salt (NS) diet cohort (8/15, p < 0.05). Further, HS plus anti-CTLA4 mAb caused an increased expression of inflammatory cytokines (IFNγ and IL-1β) in lung infiltrating and peripheral circulating CD4+T cells. This inflammatory activation of CD4+T cells in the HS plus anti-CTLA4 cohort was associated with the upregulation of inflammasome complex activity. However, an LS diet did not induce any significant irAE response in breast-tumor-bearing mice upon treatment with anti-CTLA4 mAb, thus suggesting the role of high-salt diet in irAE response. Importantly, CD4-specific knock out of osmosensitive transcription factor NFAT5 using CD4cre/creNFAT5flox/flox transgenic mice caused a downregulation of high-salt-mediated inflammatory activation of CD4+T cells and irAE response. Taken together, our data suggest that LS diet inhibits the anti-CTLA4 mAb-induced irAE response while retaining its anti-tumor efficacy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Low-Salt Diet Reduces Anti-CTLA4 Mediated Systemic Immune-Related Adverse Events while Retaining Therapeutic Efficacy against Breast Cancer

Khandekar

Dahunsi

Esteve

et al. 2022

Biology

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“…86 However, given that high salt intake is a potent inducer of proinflammatory states, the adverse effect of HSD on cancer has also been reported. 212 In vitro, high salt can synergize with IL-17 to enhance the proliferation, treatment resistance and Warburg-like metabolism of breast cancer cells. [213][214][215] In mice, an HSD accelerated the development and lung metastasis of breast cancer.…”

Section: Cancermentioning

confidence: 99%

The modulatory effect of high salt on immune cells and related diseases

Alu

Wei

et al. 2022

Cell Proliferation

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Background: The adverse effect of excessive salt intake has been recognized in decades. Researchers have mainly focused on the association between salt intake and hypertension. However, studies in recent years have proposed the existence of extra-renal sodium storage and provided insight into the immunomodulatory function of sodium.Objectives: In this review, we discuss the modulatory effects of high salt on various innate and adaptive immune cells and immune-regulated diseases. Methods: We identified papers through electronic searches of PubMed database from inception to March 2022. Results: An increasing body of evidence has demonstrated that high salt can modulate the differentiation, activation and function of multiple immune cells. Furthermore, a high-salt diet can increase tissue sodium concentrations and influence the immune responses in microenvironments, thereby affecting the development of immune-regulated diseases, including hypertension, multiple sclerosis, cancer and infections. These findings provide a novel mechanism for the pathology of certain diseases and indicate that salt might serve as a target or potential therapeutic agent in different disease contexts. Conclusion: High salt has a profound impact on the differentiation, activation and function of multiple immune cells. Additionally, an HSD can modulate the development of various immune-regulated diseases. | INTRODUCTIONSalt (NaCl), common in our daily life, can be found naturally in various foods and is used in food manufacturing, the chemical industry, clinical therapy and so forth. For instance, salty condiments contain plenty of NaCl, whereas saline is the most frequently administered intravenous fluid. 1 Although salt is necessary for the human body, excessive salt intake can be detrimental and increase the risk of diseases such as hypertension, heart failure and renal disease. 2 In addition, the immunomodulatory function of salt has been reported. Early studies found that high salt increased the cytokine production in peripheral blood mononuclear cells (PBMCs). 3,4 In the past decades, growing evidence has indicated that high salt can influence various immune cells. Moreover, a high-salt diet (HSD) has a pronounced effect on immuneregulated diseases, and salt is potentially applied in immune therapy. This review will summarize some of the recent advances in the

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“…Nevertheless, despite the potential benefits of salt intake on cancer treatment effectiveness, high salt intake can also lead to the development of a proinflammatory state, which can negatively impact cancer outcomes. 188 High salt intake is a risk factor for various types of cancer in humans, including lung, testicular, bladder, renal cell, pancreatic, esophageal, and gastric cancer. 182 HSD has been shown to induce chronic inflammation, which may in turn incite continuous cell proliferation, DNA damage, or cancer transformation.…”

Section: Targeted Dietary Interventions and Mechanistic Insights Into...mentioning

confidence: 99%

“…However, whether there is a connection remains uncertain. 188 IL-17, specifically IL-17A, plays an important role in the mechanism of action of HSD. Evidence suggests that high salt intake can induce the differentiation of Th17 cells, a prominent source of IL-17A.…”

Section: Targeted Dietary Interventions and Mechanistic Insights Into...mentioning

confidence: 99%

Effects of dietary intervention on human diseases: molecular mechanisms and therapeutic potential

Xiao,

Gong,

et al. 2024

Sig Transduct Target Ther

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Diet, serving as a vital source of nutrients, exerts a profound influence on human health and disease progression. Recently, dietary interventions have emerged as promising adjunctive treatment strategies not only for cancer but also for neurodegenerative diseases, autoimmune diseases, cardiovascular diseases, and metabolic disorders. These interventions have demonstrated substantial potential in modulating metabolism, disease trajectory, and therapeutic responses. Metabolic reprogramming is a hallmark of malignant progression, and a deeper understanding of this phenomenon in tumors and its effects on immune regulation is a significant challenge that impedes cancer eradication. Dietary intake, as a key environmental factor, can influence tumor metabolism. Emerging evidence indicates that dietary interventions might affect the nutrient availability in tumors, thereby increasing the efficacy of cancer treatments. However, the intricate interplay between dietary interventions and the pathogenesis of cancer and other diseases is complex. Despite encouraging results, the mechanisms underlying diet-based therapeutic strategies remain largely unexplored, often resulting in underutilization in disease management. In this review, we aim to illuminate the potential effects of various dietary interventions, including calorie restriction, fasting-mimicking diet, ketogenic diet, protein restriction diet, high-salt diet, high-fat diet, and high-fiber diet, on cancer and the aforementioned diseases. We explore the multifaceted impacts of these dietary interventions, encompassing their immunomodulatory effects, other biological impacts, and underlying molecular mechanisms. This review offers valuable insights into the potential application of these dietary interventions as adjunctive therapies in disease management.

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Cancer Salt Nostalgia

Cited by 9 publications

References 89 publications

Low-Salt Diet Reduces Anti-CTLA4 Mediated Systemic Immune-Related Adverse Events while Retaining Therapeutic Efficacy against Breast Cancer

Low-Salt Diet Reduces Anti-CTLA4 Mediated Systemic Immune-Related Adverse Events while Retaining Therapeutic Efficacy against Breast Cancer

The modulatory effect of high salt on immune cells and related diseases

Effects of dietary intervention on human diseases: molecular mechanisms and therapeutic potential

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