Interactions between MDSCs and the Autonomic Nervous System: Opportunities and Challenges in Cancer Neuroscience.

Myeloid-derived suppressor cells (MDSC) are a population of heterogeneous immune cells that are involved in precancerous conditions and neoplasms. The autonomic nervous system (ANS), which is composed of the sympathetic nervous system and the parasympathetic nervous system, is an important component of the tumor microenvironment that responds to changes in the internal and external environment mainly through adrenergic and cholinergic signaling. An abnormal increase of autonomic nerve density has been associated with cancer progression. As we discuss in this review, growing evidence indicates that sympathetic and parasympathetic signals directly affect the expansion, mobilization, and redistribution of MDSCs. Dysregulated autonomic signaling recruits MDSCs to form an immunosuppressive microenvironment in chronically inflamed tissues, resulting in abnormal proliferation and differentiation of adult stem cells. The two components of the ANS may also be responsible for the seemingly contradictory behaviors of MDSCs. Elucidating the underlying mechanisms has the potential to provide more insights into the complex roles of MDSCs in tumor development and lay the foundation for the development of novel MDSC-targeted anticancer strategies.

Dysbiosis promotes recurrence of adenomatous polyps in the distal colorectum.

BACKGROUND: Colorectal polyps, which are characterized by a high recurrence rate, represent preneoplastic conditions of the intestine. Due to unclear mechanisms of pathogenesis, first-line therapies for non-hereditary recurrent colorectal polyps are limited to endoscopic resection. Although recent studies suggest a mechanistic link between intestinal dysbiosis and polyps, the exact compositions and roles of bacteria in the mucosa around the lesions, rather than feces, remain unsettled. AIM: To clarify the composition and diversity of bacteria in the mucosa surrounding or 10 cm distal to recurrent intestinal polyps. METHODS: Mucosal samples were collected from four patients consistently with adenomatous polyps (Ade), seven consistently with non-Ade (Pol), ten with current Pol but previous Ade, and six healthy individuals, and bacterial patterns were evaluated by 16S rDNA sequencing. Linear discriminant analysis and Student's t-tests were used to identify the genus-level bacteria differences between groups with different colorectal polyp phenotypes. Pearson's correlation coefficients were used to evaluate the correlation between intestinal bacteria at the genus level and clinical indicators. RESULTS: The results confirmed a decreased level of probiotics and an enrichment of pathogenic bacteria in patients with all types of polyps compared to healthy individuals. These changes were not restricted to the mucosa within 0.5 cm adjacent to the polyps, but also existed in histologically normal tissue 10 cm distal from the lesions. Significant differences in bacterial diversity were observed in the mucosa from individuals with normal conditions, Pol, and Ade. Increased abundance of Gram-negative bacteria, including Klebsiella, Plesiomonas, and Cronobacter, was observed in Pol group and Ade group, suggesting that resistance to antibiotics may be one risk factor for bacterium-related harmful environment. Meanwhile, age and gender were linked to bacteria changes, indicating the potential involvement of sex hormones. CONCLUSION: These preliminary results support intestinal dysbiosis as an important risk factor for recurrent polyps, especially adenoma. Targeting specific pathogenic bacteria may attenuate the recurrence of polyps.