Mushroom Compounds Activate Immune Cells to Fight Cancer

Jim Crocker
25th February, 2024

Image Source: Natural Science News, 2024

In the ongoing battle against cancer, scientists are constantly seeking new ways to harness the body's immune system to fight tumor cells. A promising avenue of research involves activating the immune system's first line of defense: macrophages. These cells, which are part of the innate immune system, can be coaxed into attacking cancer cells. Researchers from the University of Oslo have made a significant breakthrough in this area by identifying certain substances that can turn macrophages into cancer-fighting agents^[1]. Macrophages are versatile cells that can either support or combat tumor growth. In many cancers, they are manipulated by the tumor to aid its growth and spread. However, when activated correctly, macrophages can become tumoricidal, meaning they can kill tumor cells. The key to this transformation lies in their ability to recognize specific patterns through receptors on their surface, known as pattern recognition receptors (PRRs). These receptors can detect certain molecules that are commonly found on pathogens—or in this case, on cancer cells—and trigger an immune response. The study from the University of Oslo focused on substances called polysaccharides, which are long chains of sugar molecules, derived from the medicinal fungus Inonotus obliquus. The researchers discovered two specific water-soluble polysaccharides, named AcF1 and AcF3, that have the ability to activate macrophages and induce them to produce substances that are toxic to cancer cells, such as nitric oxide, tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). These activated macrophages also produce interleukin-12p70 (IL-12p70) when combined with another immune signaling molecule, interferon-γ. IL-12p70 is crucial for antitumor immunity because it helps to orchestrate the attack of the adaptive immune system, which includes the T cells that can specifically target and destroy cancer cells. This finding ties in with previous research that showed the importance of macrophage-derived chemokines in recruiting T cells to the tumor site, which is essential for the success of certain immunotherapies^[2]. Interestingly, AcF1 and AcF3 were found to be strong agonists of TLR2 and TLR4, which are types of PRRs. An agonist is a substance that activates a receptor to produce a biological response. This activation leads to the macrophages' antitumor functions. This discovery aligns with earlier studies that have highlighted the potential of TLR agonists as immunological adjuvants to restore cancer immunosurveillance^[3]. It also supports the development of therapies that target these receptors to stimulate specific anticancer immune responses within the tumor microenvironment. In contrast, other substances tested in the study, such as particulate β-glucans from both I. obliquus and Saccharomyces cerevisiae (zymosan), were found to be agonists for Dectin-1, another PRR, but not for TLR2 or TLR4. These substances did not trigger the antitumor functions of macrophages, highlighting the specificity required for effective immunomodulation. The findings from the University of Oslo suggest that AcF1 and AcF3 have strong potential for use in cancer immunotherapy. By activating multiple PRRs and inducing potent antitumor activity in macrophages, these fungal polysaccharides could be key players in the development of new treatments. This research builds upon previous studies that have explored the dual nature of macrophages in cancer, showing that they can be reprogrammed from a tumor-promoting to a tumor-fighting state^[4]. It also resonates with the design of new, safe, and specific TLR agonists that can reorient macrophages towards an anti-tumor phenotype^[5]. The implications of this research are significant. By understanding how to manipulate macrophages to fight cancer, scientists can develop therapies that may improve the efficacy of existing treatments, such as immune checkpoint blockade, and potentially lead to more successful outcomes for patients. The study from the University of Oslo is a step forward in the quest to harness the power of the immune system in the fight against cancer.

Medicine Biochem Mycology