Pancreatic ductal adenocarcinoma (PDAC) is an incurable cancer resistant to traditional treatments, although a limited number of early-stage patients can undergo radical resection. Immunotherapies for the treatment of haematological malignancies as well as solid tumours have been substantially improved over the past decades, and impressive results have been obtained in recent preclinical and clinical trials. However, PDAC is likely the exception because of its unique tumour microenvironment (TME). In this review, we summarize the characteristics of the PDAC TME and focus on the network of various tumour-infiltrating immune cells, outlining the current advances in PDAC immunotherapy and addressing the effect of the PDAC TME on immunotherapy. This review further explores the combinations of different therapies used to enhance antitumour efficacy or reverse immunodeficiencies and describes optimizable immunotherapeutic strategies for PDAC. The concordant combination of various treatments, such as targeting cancer cells and the stroma, reversing suppressive immune reactions and enhancing antitumour reactivity, may be the most promising approach for the treatment of PDAC. Traditional treatments, especially chemotherapy, may also be optimized for individual patients to remodel the immunosuppressive microenvironment for enhanced therapy.

Administration of LBB modulates the gut microbiota and reduces colon cancer development by decreasing tumor incidence, multiplicity/count, and volume via enhanced TLR2-improved gut mucosa epithelial barrier integrity and suppression of apoptosis and inflammation.

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Acute cholecystitis (AC) is one of the most common surgical diseases. Bacterial infection accounts for 50% to 85% of the disease's onset. Since there is a close relationship between the biliary system and the gut, the aims of this study were to characterize and determine the influence of gut microbiota on AC, to detect the pathogenic microorganism in the biliary system, and to explore the relationship between the gut and bile microbiota of patients with AC. A total of 185 713 high-quality sequence reads were generated from the faecal samples of 15 patients and 13 healthy controls by 16S rRNA gene pyrosequencing. Patients' samples were significantly enriched in Akkermansia, Enterobacter and Escherichia/Shigella group. The healthy controls, however, showed significant enrichment of Clostridiales, Coprococcus, Coprobacillaceae, Paraprevotella, Turicibacter and TM7-3 in their faecal samples. Escherichia coli was the main biliary pathogenic microorganism, among others such as Klebsiella spp., Clostridium perfringens, Citrobacter freundii and Enterobacter cloacae in the bile of the patients. Additionally, the amount of bile endotoxin significantly correlated with the number of Enterobacteriaceae, especially E. coli. Our data indicate that Enterobacteriaceae might play essential role in the pathogenesis and/or progress of AC. This was verified in an in vivo model using a pathogenic E. coli isolated from one of the patients in guinea pigs and observed marked gallbladder inflammation and morphologic changes. This study thus provides insight which could be useful for the prevention, diagnosis and treatment of AC and related diseases by controlling the growth of Enterobacteriaceae to alleviate the infection.

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Pancreatitis is an inflammatory disease that is responsible for substantial morbidity and mortality, and it can induce pancreatic necrosis that starts within pancreatic acinar cells in severe cases. Emodin, a pleiotropic natural product isolated from the Chinese herb Rheum palmatum L., has effective anti-inflammatory activities. In this paper, we investigated the protective effects and molecular mechanism of emodin against sodium taurocholate (STC)-induced pancreatic acinar cells injury in vitro and in vivo; and the results showed that emodin could significantly alleviate STC-induced pancreatic acinar cells injury through decreasing trypsin, amylase and the release of inflammatory factors (tumor necrosis factor alpha, interleukin-1β, and interleukin-6). Also, we found that emodin could significantly downregulate the HTRA1, interleukin-33, myeloid differentiation primary response gene 88, TNF receptor-associated factor-6, and nuclear factor kappa-B protein levels, but upregulate the transforming growth factor beta 1 (TGF-β1) protein level. These results indicated that emodin alleviated pancreatic acinar cells injury mainly through inhibiting HTRA1/TGF-β1 signaling pathway, and this finding was further proved by the HTRA1 overexpression experiments. In addition, the inflammatory regulator microRNA-30a-5p (miR-30a-5p) was confirmed to be a transcriptional brake that controls the HTRA1 gene through using a dual luciferase reporter assay, and it was upregulated by emodin in pancreatic acinar cells. Furthermore, the pancreatic protective effects and anti-inflammatory activities of emodin were all abrogated with both miR-30a-5p inhibitor in vitro and miR-30a-5p antagomir in vivo. Collectively, these results demonstrate that miR-30a-5p/HTRA1 are the target of emodin-mediated attenuation of pancreatic acinar cell injury in pancreatitis, thus providing the foundation for further development of this natural product for medical therapy.