Yeast-Derived β-Glucan in Cancer: Novel Uses of a Traditional Therapeutic.

Anne Geller,Rejeena Shrestha,Jun Yan

doi:10.3390/ijms20153618

Anne Geller, Rejeena Shrestha + Show 1 more

Open Access

https://doi.org/10.3390/ijms20153618

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Abstract

An increased understanding of the complex mechanisms at play within the tumor microenvironment (TME) has emphasized the need for the development of strategies that target immune cells within the TME. Therapeutics that render the TME immune-reactive have a vast potential for establishing effective cancer interventions. One such intervention is β-glucan, a natural compound with immune-stimulatory and immunomodulatory potential that has long been considered an important anti-cancer therapeutic. β-glucan has the ability to modulate the TME both by bridging the innate and adaptive arms of the immune system and by modulating the phenotype of immune-suppressive cells to be immune-stimulatory. New roles for β-glucan in cancer therapy are also emerging through an evolving understanding that β-glucan is involved in a concept called trained immunity, where innate cells take on memory phenotypes. Additionally, the hollow structure of particulate β-glucan has recently been harnessed to utilize particulate β-glucan as a delivery vesicle. These new concepts, along with the emerging success of combinatorial approaches to cancer treatment involving β-glucan, suggest that β-glucan may play an essential role in future strategies to prevent and inhibit tumor growth. This review emphasizes the various characteristics of β-glucan, with an emphasis on fungal β-glucan, and highlights novel approaches of β-glucan in cancer therapy.

Highlights

Though fungi did not emerge as a major pathogen for mammals until the late 20th century, animals have been fighting the harmful effects of fungi for millennia, and, over the course of evolution have evolved robust innate immune responses to components of the fungal cell wall, such as β-glucan [1,2]
Injection of the nanoparticles into Balb/c mice bearing 4T1 mammary tumors resulted in migration inhibitory factor (MIF) reduction in tumor-associated macrophages (TAM)
Oral gavage of mice with glucan encapsulated siRNA particles (GeRPs) containing as little as 20 μg kg−1 siRNA directed against TNFα depleted its messenger RNA in macrophages recovered from the peritoneum, spleen, liver and lung, and lowered serum

Summary

Introduction

Though fungi did not emerge as a major pathogen for mammals until the late 20th century, animals have been fighting the harmful effects of fungi for millennia, and, over the course of evolution have evolved robust innate immune responses to components of the fungal cell wall, such as β-glucan [1,2]. Differences in molecular weight, degree of branching, polymeric charge and solution conformation affect the degree of triple helical formation, which affects the solubility of β-glucan Together these variables can cause β-glucans isolated from the same source to take on drastically different immune-modulating properties [17,27,30]. Many scientists use extraction techniques involving the use of high or low pH and temperature conditions which can lead to denatured or renatured molecules that may have a different conformation and different immune-stimulatory properties [31,32] For this reason, a great deal of care must be taken to isolate and purify β-glucan, and to confirm the purity status of these extracts before use and throughout experimenation. It becomes important to clearly and meticulously define and report the source of β-glucans used in scientific research and to catalog the preparation and treatment of all samples used

The Trafficking of β-Glucan

Transcriptional Changes Induced by β-Glucan

Results of Study

Conclusions