The key role of intestinal microethics in inflammatory-driven colorectal cancer has been revealed

is the largest micro-ecosystem in the human body, with more than 1000 kinds of microorganisms, accounting for 78% of the total amount of microorganisms in the human body. Interestingly, the intestinal mucous membranes build up about 60% to 70% of the body's immune cells, becoming a natural barrier to maintaining human health and the body's "largest" immune organ.
study showed that chronic inflammation of the intestines increased the incidence of colorectal cancer. Inflammatory bowel disease, especially ulcerative colitis, has been identified as a susceptible factor to colorectal cancer. In recent years, scholars have paid attention to abnormal intestinal micro-ecology as one of the important factors that cause colorectal cancer, but the specific reasons need to be clarified.
, Gastroenterology published online the latest research results obtained by Qiu Fuming, a professor at Zhejiang University's Second Hospital and Zhejiang Cancer Micro-Environment and Immunotherapy Key Laboratory, in cooperation with Huang Jian's team, revealing the important role of bacteriologic-immune interoperability in the occurrence of enteritis-related tumors.2015, the team, led by Huang Jian, discovered the important immunosuppressive role of polycyte-based myelin-suppressing cells in the inflammatory micro-environment of colorectal cancer in humans, and the research was published in the journal Immunology in the form of a cover paper.
tumor micro-environment, macrophages play an important role in addition to multi-nucleocyte-inhibiting cells.
years, a number of treatment strategies targeting tumor-related macrophages have entered preclinical and clinical phase 1 trials, but the efficacy is limited. Scholars have found that changes in tumor-immersed macrophage function are determined by different sub-groups, so macrophage heterogeneity is an important factor in limiting the clinical transformation of targeted macrophages.
In order to depict the dynamic evolution of macrophages in the occurrence of enteritis-related tumors, the researchers built a mouse enteritis-related tumor model and found that monocyte-like macrophages were specifically rich in the early stages of enteritis-related tumors. As a sub-group of macrophages, monocyte-like macrophages have the effect of strong secretion of inflammatory factors, and their quantitative changes have a profound effect on the nature and function of macrophages as a whole.
team found that reducing the build-up of monocyte-like macrophages into the intestines during the tumor's non-formation phase significantly reduced tumor load, suggesting that monocyte-like macrophages may be potential therapeutic targets.
explores macrophages at different stages before tumor formation, and can identify specific macrophage sub-groups, which in turn can affect tumor formation by interfering with these cells. Huang Jian introduced that this research can give us a better understanding of tumor formation mechanism, provide the possibility of tumor treatment targeting heterogeneity macrophage sub-groups, and guide new ideas and strategies for future clinical transformation.why monocyte-like macrophages are rich in the early stages of enteritis-related tumors, what exactly is the order?
human microbiome as the "hero" in the intestines, has been widely concerned. Although previous studies have extensively explored the relationship between the gut microbiome and cancer, little is known about how gut bacteria work together with immune cells to affect enteritis-related tumor formation.
interestingly, when researchers used antibiotics to deplete gut bacteria, the number of intestinal monocyte-like macrophages decreased significantly and the occurrence of intestinal tumors decreased significantly. Further analysis of the cause, the team found that the level of CCL2, the cogeneration factor responsible for recruiting monocyte-like macrophages, decreased.
"We're trying to figure out why mice treated with antibiotics produce less CCL2 in their intestines. Qiu Fuming said, "When we found that lipid polysaccharies can regulate the expression of intestinal epithelitis CCL2, we realized that this would be a very critical entry point." "In further experiments, the researchers found that antibiotic use reduced lipid polysaccharine levels, and that increased lipid polysaccharose levels could alter the number of monocyte-like macrophages in the gut, which in turn could affect inflammation and tumors.
previous studies have shown a significant increase in lipid polysaccharine levels in bowel cancer tissue, as well as abnormal activation of a variety of lipid polysaccharine-related signaling path pathps. The researchers expanded their research and found that lipid polysaccharides not only regulate the number of monocyte-like macrophages, but also further promote their activity and secrete related cytokines leading to the accumulation of interletin 17 auxiliary T cells in the intestines. The production of interlebin 17 auxiliary T cells has been reported to play a vital role in the development of tumors.these mechanisms are not only present in mice, but may also be valid in humans, the researchers said.
Compared to healthy people, there was an increase in lipid polysaccharide bacteria in the intestines of patients with ulcerative colitis and colorectal cancer, and in combination with transcriptional data from healthy subjects, ulcerative colitis and enteritis-related colorectal tumor patients, the researchers further found that the interaction of immune cells with bacterial products formed the core of the network of intracous interactions within tumors.
From early animal models to the discovery of a class of macrophage subpopulations that affect tumors, and from its over-collection to derive a brand-new bacterial group regulation loop, the research team after three years, the analysis of a complete bacteripology-immune interoperability to promote the development of enteritis-related tumors mechanism.
"Many studies have shown a link between gut bacteria and tumor development, but this study not only identifies a correlation, but more importantly, describes how bacteria regulate tumor occurrence by acting on intestinal immune responses," said Qiu, who said the study provides a scientific basis for clarifying the potential mechanisms of bacteriologic-immune interoperability in human enteritis-related tumors and provides ideas for developing immunotherapy based on joint target micro-ecological and micro-environmental. (Source: Cui Xueqin, China Science Daily)
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