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

• Published in: Cancer Immunology, Immunotherapy Immunotherapy, 2018-11, Vol.67 (11), p.1731-1742
• Main Authors: Alexander, Matthew P., Fiering, Steven N., Ostroff, Gary R., Cramer, Robert A., Mullins, David W.
• Format: Article
• Language: English
• Subjects: Adaptive immunity; Adaptive Immunity - immunology; Adjuvants, Immunologic; Animals; Antitumor activity; beta-Glucans - pharmacology; Cancer Research; Complement receptor 3; Cytotoxicity; Hypoxia-Inducible Factor 1, alpha Subunit - physiology; Immunology; Immunostimulation; Inflammation; Inflammation Mediators - immunology; Inflammation Mediators - metabolism; Lung Neoplasms - drug therapy; Lung Neoplasms - immunology; Lung Neoplasms - metabolism; Lung Neoplasms - secondary; Lymphocytes T; Macrophage colony-stimulating factor; Malignancy; Medicine; Medicine & Public Health; Melanoma; Melanoma, Experimental - drug therapy; Melanoma, Experimental - immunology; Melanoma, Experimental - metabolism; Melanoma, Experimental - pathology; Metastases; Metastasis; Mice; Mice, Inbred C57BL; Mice, Knockout; Monocyte chemoattractant protein 1; Monocytes; Monocytes - drug effects; Monocytes - immunology; Monocytes - metabolism; Oncology; Original; Original Article; Polysaccharides; Receptors, CCR2 - physiology; T cell receptors; T-Lymphocytes - immunology; Tumor cells; Tumor Cells, Cultured; Tumor necrosis factor-α; β-Glucan
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-018-2234-9

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.