Immunosuppressive activity is attenuated by Astragalus polysaccharides through remodeling the gut microenvironment in melanoma mice.

Abstract

Astragalus polysaccharides (APS), the main effective component of Astragalus membranaceus, can inhibit tumor growth, but the underlying mechanisms remain unclear. Previous studies have suggested that APS can regulate the gut microenvironment, including the gut microbiota and fecal metabolites. In this work, our results showed that APS could control tumor growth in melanoma-bearing mice. It could reduce the number of myeloid-derived suppressor cells (MDSC), as well as the expression of MDSC-related molecule Arg-1 and cytokines IL-10 and TGF-β, so that CD8+ T cells could kill tumor cells more effectively. However, while APS were administered with an antibiotic cocktail (ABX), MDSC could not be reduced, and the growth rate of tumors was accelerated. Consistent with the changes in MDSC, the serum levels of IL-6 and IL-1β were lowest in the APS group. Meanwhile, we found that fecal suspension from mice in the APS group could also reduce the number of MDSC in tumor tissues. These results revealed that APS regulated the immune function in tumor-bearing mice through remodeling the gut microbiota. Next, we focused on the results of 16S rRNA, which showed that APS significantly regulated most microorganisms, such as Bifidobacterium pseudolongum, Lactobacillus johnsonii and Lactobacillus. According to the Spearman analysis, the changes in abundance of these microorganisms were related to the increase of metabolites like glutamate and creatine, which could control tumor growth. The present study demonstrates that APS attenuate the immunosuppressive activity of MDSC in melanoma-bearing mice by remodeling the gut microbiota and fecal metabolites. Our findings reveal the therapeutic potential of APS to control tumor growth.

• Authors: Guiqing Ding, Qianyi Gong, Jinyun Ma, Xiaojun Liu, Yuanhua Wang, Xiaodong Cheng
• Journal: Cancer science (Cancer Sci) Vol. 112 Issue 10 Pg. 4050-4063 (Oct 2021) ISSN: 1349-7006 [Electronic] England
• PMID: 34289209 (Publication Type: Journal Article)
• Copyright: © 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Chemical References

• Anti-Bacterial Agents
• Drug Combinations
• Interleukin-1beta
• Interleukin-6
• Polysaccharides
• RNA, Ribosomal, 16S
• Transforming Growth Factor beta
• interleukin-6, mouse
• Interleukin-10
• Arg1 protein, mouse
• Arginase

Topics

• Animals
• Anti-Bacterial Agents (administration & dosage)
• Arginase (drug effects, metabolism)
• Astragalus Plant (chemistry)
• Bifidobacterium (drug effects, metabolism)
• CD8-Positive T-Lymphocytes (immunology)
• Drug Combinations
• Fecal Microbiota Transplantation
• Feces (microbiology)
• Gastrointestinal Microbiome (drug effects, genetics, immunology, physiology)
• Immune Tolerance
• Interleukin-10 (metabolism)
• Interleukin-1beta (blood)
• Interleukin-6 (blood)
• Lactobacillus (drug effects)
• Male
• Melanoma (drug therapy, immunology, pathology)
• Mice
• Mice, Inbred C57BL
• Myeloid-Derived Suppressor Cells (drug effects, immunology, metabolism)
• Polysaccharides (pharmacology)
• RNA, Ribosomal, 16S (analysis)
• Transforming Growth Factor beta (drug effects, metabolism)
• Tumor Microenvironment (immunology)