Mushroom Compounds Activate Immune Cells to Fight Cancer

Jim Crocker
25th February, 2024

Mushroom Compounds Activate Immune Cells to Fight Cancer

Chaga (Inonotus obliquus)

Photographer: Trix Niernberger
The immune system’s role in fighting cancer is a complex and evolving area of research. For decades, scientists have debated whether the immune system actively prevents cancer development, or simply deals with it after it arises[2]. Evidence suggests both are true – a functioning immune system can identify and eliminate cancerous or pre-cancerous cells, and a weakened immune system increases cancer risk[2]. This research focuses on harnessing the power of the immune system, specifically macrophages, to combat cancer, using compounds derived from a medicinal fungus. Researchers at the University of Oslo investigated the potential of polysaccharides – complex carbohydrates – extracted from Inonotus obliquus, commonly known as Chaga mushroom, to stimulate anti-cancer activity in macrophages. Macrophages are a type of white blood cell that engulfs and destroys cellular debris, foreign substances, and, importantly, cancer cells. However, macrophages can also sometimes promote tumor growth, depending on the signals they receive[3]. The goal of this study[1] was to identify specific polysaccharides that could reliably push macrophages towards an anti-cancer state. The study identified six polysaccharides from Inonotus obliquus. Two of these, named AcF1 and AcF3, demonstrated a significant ability to activate macrophages in both mice and humans. Activation meant the macrophages began to produce nitric oxide, a molecule toxic to cancer cells, and pro-inflammatory cytokines – signaling molecules that help coordinate an immune response. Specifically, AcF1 and AcF3, when combined with interferon-gamma (IFNγ), a cytokine known to enhance immune function, triggered high levels of IL-12p70. IL-12p70 is crucial for developing effective anti-tumor immunity[4]. In laboratory tests, these activated macrophages directly inhibited the growth of cancer cells. The mechanism behind this activation involves pattern recognition receptors (PRRs) on the surface of macrophages. PRRs are like sensors that detect specific molecules associated with pathogens or cellular damage. AcF1 and AcF3 were found to strongly activate two PRRs: Toll-like receptor 2 (TLR2) and TLR4. They also showed some activation of Dectin-1. This is significant because other fungal compounds, like β-glucans from Inonotus obliquus and Saccharomyces cerevisiae (yeast), primarily activate Dectin-1 but don’t trigger the same anti-cancer functions in macrophages. This suggests that TLR2 and TLR4 activation is particularly important for stimulating an effective anti-tumor response. The importance of T lymphocytes in cancer immunotherapy is well established[5], but this study highlights the crucial role of macrophages as well. The activation of macrophages by CD4+ T cells, through the release of IFNγ, is a known mechanism for tumor suppression[4]. The polysaccharides AcF1 and AcF3 appear to act upstream of this process, directly activating macrophages and priming them to respond more effectively to signals from T cells. The findings build on the understanding that the immune system can play a preventative role in cancer[2]. By identifying compounds that specifically enhance the anti-tumor activity of macrophages, this research offers a potential new avenue for cancer immunotherapy – treatment that uses the body’s own immune system to fight cancer. The ability of AcF1 and AcF3 to activate multiple PRRs and induce potent anti-cancer activity suggests they have strong potential as therapeutic agents.

MedicineBiochemMycology

References

Main Study

1) Fungal polysaccharides from Inonotus obliquus are agonists for Toll-like receptors and induce macrophage anti-cancer activity.

Published 23rd February, 2024

https://doi.org/10.1038/s42003-024-05853-y

Related Studies

2) Does the immune system naturally protect against cancer?

https://doi.org/10.3389/fimmu.2014.00197

3) Role of tumor-associated macrophages in human malignancies: friend or foe?

https://doi.org/10.1111/pin.12440

4) Primary antitumor immune response mediated by CD4+ T cells.

Journal: Immunity, Issue: Vol 22, Issue 3, Mar 2005

5) A guide to cancer immunotherapy: from T cell basic science to clinical practice.

https://doi.org/10.1038/s41577-020-0306-5


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