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Rhodes2019 - Immune-Mediated theory of Metastasis

ABSTRACT: Abstract: Accumulating experimental and clinical evidence suggest that the immune response to cancer is not exclusively anti-tumor. Indeed, the pro-tumor roles of the immune system - as suppliers of growth and pro-angiogenic factors or defenses against cytotoxic immune attacks, for example - have been long appreciated, but relatively few theoretical works have considered their effects. Inspired by the recently proposed "immune-mediated" theory of metastasis, we develop a mathematical model for tumor-immune interactions at two anatomically distant sites, which includes both anti- and pro-tumor immune effects, and the experimentally observed tumor-induced phenotypic plasticity of immune cells (tumor "education" of the immune cells). Upon confrontation of our model to experimental data, we use it to evaluate the implications of the immune-mediated theory of metastasis. We find that tumor education of immune cells may explain the relatively poor performance of immunotherapies, and that many metastatic phenomena, including metastatic blow-up, dormancy, and metastasis to sites of injury, can be explained by the immune-mediated theory of metastasis. Our results suggest that further work is warranted to fully elucidate the pro-tumor effects of the immune system in metastatic cancer.

SUBMITTER: Szeyi Ng

PROVIDER: BIOMD0000000926 | BioModels | 2024-09-02

REPOSITORIES: BioModels

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			Action	DRS
	BIOMD0000000926?filename=Rhodes2019-Immune-Mediated%20theory%20of%20Metastasis.cps	Other
	BIOMD0000000926?filename=Rhodes2019-Immune-Mediated%20theory%20of%20Metastasis.xml	Xml
	BIOMD0000000926?filename=Rhodes2019-Immune-Mediated%20theory%20of%20Metastasis_V1.cps	Other
	BIOMD0000000926?filename=Rhodes2019-Immune-Mediated%20theory%20of%20Metastasis_V1.sedml	Other
	BIOMD0000000926?filename=Rhodes2019-Immune-Mediated%20theory%20of%20Metastasis_V1.xml	Xml

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Project description:Difference in salt concentration may cause dramatic alterations in tumor microenvironment, progression of cancer and overall outcome of cancer therapy. Immune cells in tumor microenvironment are mostly immunosuppressed under the influence of tumor cells. Recent studies has shown that high salt induces immune cells to pro-inflammatory state in the tumor microenvironment. On contrary, it hinders the immunosuppressive functions of regulatory T cells, which plays an important role in inhibiting anti-cancer immune responses in tumor microenvironment. Salt- mediated induction of the immune cells to pro-inflammatory state could potentially enhance their transition from the immunosuppressed state to their innate pro- inflammatory state, thereby facilitating their effectiveness in combating the tumor and suppressing tumor progression. The role of high salt in cancer is controversial with only a few studies suggesting the potential pro-tumorigenic effect of high salt. Dietary salt increased the risk of gastric cancer, contributing to both the incidence and mortality of the disease by damaging the gastric mucosal lining. Another research indicated that a high salt diet could stimulate the growth of breast cancer and promote lung metastasis by elevating Th17 cell levels. In contrast, high salt containing diets significantly inhibited tumor growth, primarily through the depletion and functional modulation of myeloid-derived suppressor cells (MDSCs), highlighting its anti-cancer efficacy. High salt reduced cytokine production necessary for the expansion of myeloid-derived suppressor cells (MDSCs) and decreases MDSC accumulation in blood, spleen, and tumors. High salt diet in mice also showed increased Bifidobacterium abundance and heightened gut permeability, leading to intratumor localization of Bifidobacterium and enhancing NK cell functions. This facilitated tumor regression, suggesting potential role of high salt in cancer immunotherapy. The overall impact of high-salt diets is not fully understood, which necessitates further research to elucidate their influence in altering tumor microenvironment and fate of cancer cells. This study aimed to investigate the effects of high salt on a triple-negative breast cancer cell line (in vitro), exploring its impact on cancer progression and associated global transcriptomic changes.

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Rhodes2019 - Immune-Mediated theory of Metastasis

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