Antitumor Activity of Extract From the Sporoderm-Breaking Spore of Ganoderma lucidum: Restoration on Exhausted Cytotoxic T Cell With Gut Microbiota Remodeling

Abstract

As breast cancer is the leading cause of cancer-related deaths in women population worldwide, ongoing endeavor has been made for alternative regimens with improved efficacy but fewer adverse effects. Recently, active components from the spores of Ganoderma lucidum have attracted much attention for their versatile biological activities owing to the advance in sporoderm-breaking technology. Here, anticancer potential of an extract derived from the sporoderm-breaking spores of G. lucidum (ESG) was explored in a 4T1-breast cancer xenograft mice model. Results showed that ESG was able to suppress 4T1 tumor growth in vivo rather than in vitro. Flowcytometry analysis revealed that ESG could significantly increase both cytotoxic T cell (Tc) population and the ratio of Tc to helper T cell (Th) in peripheral blood of the tumor-bearing mouse; similar promotion on Tc was also found in tumor-infiltrating lymphocyte. Moreover, ESG evidently downregulated the two immune checkpoints, programmed cell death protein-1 (PD-1, in the spleen) and cytotoxic T lymphocyte antigen-4 (CTLA-4, in the tumor), suggesting that ESG could effectively restore the T cell paradigm by recovering the exhaustion status via suppressing the co-inhibitory checkpoints. By 16S rRNA gene sequence analysis on the fecal microbiota, it was found that ESG would remodeling the overall structure of the samples from tumor-bearing mice toward that of the normal counterparts, including 18 genera in 5 phyla, together with regulations on several genes that are responsible for signaling pathways involved in metabolism, cellular processes, and environmental information processing. Collectively, this study demonstrated that ESG would serve as a natural anticancer adjuvant via a restoration on the exhausted Tc, highlighting important clinical implications for the treatment of breast cancer.

Scutellarin Ameliorated Carbon Tetrachloride-Induced Chronic Liver Injury in Mice

“…Gut microbiota plays a pathogenic role in the development of many disease and modulation of the microbiome is a potential therapeutic approach for prevention of liver injury [16,17]. Moreover, in our previous work, we proved that SCU markedly modulated the gut microbiota (Table S1, Figure S1).…”

“…The sequencing library was built up with obtained products and then sequenced on a MiSeq sequencing platform (Illumina, USA). The sequencing data analysis was carried out as previously described [16]. The Chao1, Shannon and Pielou indices were calculated for α-diversity evaluation.…”

A Polysaccharide Purified From Ganoderma lucidum Acts as a Potent Mucosal Adjuvant That Promotes Protective Immunity Against the Lethal Challenge With Enterovirus A71

“…Some reports have shown that G. lucidum has an anti-tumor effects, which were attributed to the activation of the host immune response ( 26 ). Recently, Su et al found that extract from the spores of G. lucidum would serve as a antitumor adjuvant via a restoration on the exhausted ( 27 ). In 2005 and 2006, we demonstrated that PS-G could effectively accelerate the activation and maturation of immature DCs favoring a T helper 1 immune response ( 28 , 29 ).…”

Immunological Anti-Tumor Activity of Icariside I by Regulating Gut Microbiota and Its Derived Metabolites in a Melanoma Mouse Model

“…Inulin naturally sourced from chicory root ber can produce prebiotics to inhibit melanoma growth by modulating the composition and diversity of gut microbiota and enriching CD4+, CD8 + T cells and plasmacytoid DCs in mouse models [24]. Sporoderm-breaking spores of G. lucidum was also found to signi cantly modulate gut microbiota structure and composition in tumor-bearing mice and thus increasing the population of CD8 + T cells [25].…”