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01-11-2018 | Original Article

Beta-glucan-induced inflammatory monocytes mediate antitumor efficacy in the murine lung

Authors: Matthew P. Alexander, Steven N. Fiering, Gary R. Ostroff, Robert A. Cramer, David W. Mullins

Published in: Cancer Immunology, Immunotherapy | Issue 11/2018

Abstract

β-Glucan is a naturally occurring glucose polysaccharide with immunostimulatory activity in both infection and malignancy. β-Glucan’s antitumor effects have been attributed to the enhancement of complement receptor 3-dependent cellular cytotoxicity, as well as modulation of suppressive and stimulatory myeloid subsets, which in turn enhances antitumor T cell immunity. In the present study, we demonstrate antitumor efficacy of yeast-derived β-glucan particles (YGP) in a model of metastatic-like melanoma in the lung, through a mechanism that is independent of previously reported β-glucan-mediated antitumor pathways. Notably, efficacy is independent of adaptive immunity, but requires inflammatory monocytes. YGP-activated monocytes mediated direct cytotoxicity against tumor cells in vitro, and systemic YGP treatment upregulated inflammatory mediators, including TNFα, M-CSF, and CCL2, in the lungs. Collectively, these studies identify a novel role for inflammatory monocytes in β-glucan-mediated antitumor efficacy, and expand the understanding of how this immunomodulator can be used to generate beneficial immune responses against metastatic disease.

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Title: Beta-glucan-induced inflammatory monocytes mediate antitumor efficacy in the murine lung
Authors: Matthew P. Alexander
Steven N. Fiering
Gary R. Ostroff
Robert A. Cramer
David W. Mullins
Publication date: 01-11-2018
Publisher: Springer Berlin Heidelberg
Published in: Cancer Immunology, Immunotherapy / Issue 11/2018
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-018-2234-9

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