Objective To summarize the changes in the tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) in the context of immunotherapy and their impact on treatment outcomes. MethodsA systematic review of recent studies on the TME of PDAC was carried out to analyze the immune properties, intercellular interactions, and biological functions of its cellular and non-cellular components, disclose the molecular mechanisms of immunotherapy affects on the TME, explore the advancements in targeted therapy and potential biomarkers, and analyze the challenges in clinical applications and their impacts on the quality of life of patients. ResultsThe TME of PDAC exhibits highly immunosuppressive and heterogeneous characteristics, rich in diverse cells (such as pancreatic cancer cells, stellate cells, cancer-associated fibroblasts, immune cells) and non-cellular components (such as extracellular matrix). Immunotherapy is capable of regulating the immune balance in the TME and enhancing the anti-tumor response. Despite the progress made in multiple immunotherapy strategies (such as immune checkpoint inhibitors, chimeric antigen receptor cell therapy), challenges such as difficulty in selecting targets, drug resistance, and side effects still persist. Meanwhile, potential biomarkers such as leukemia inhibitory factor offer new directions for individualized treatment. ConclusionsThe TME of PDAC undergoes continuous changes during immunotherapy. In the future, it is requisite to integrate new technologies to deeply explore targets and biomarkers, optimize multimodal precise treatment strategies, enhance the safety and efficacy of immunotherapy, and improve the prognosis of patients.
ObjectiveTo detect the expression of programmed cell death ligand 1 (PD-L1) in papillary thyroid carcinoma (PTC) and PTC with coexistent Hashimoto’s thyroiditis (HT) tissues, and to explore its clinical significance of its expression.MethodsThe PTC patients who underwent thyroidectomy at the Thyroid Surgery Department of the Affiliated Hospital of Guizhou Medical University from March 2017 to May 2019 were retrospectively collected. Immunohistochemical staining was used to detect the expression of PD-L1 in the PTC tissues, PD-L1 staining positive cells ≥20% was judged as positive expression, <20% was judged as negative expression. The relationship between PD-L1 positive expression rate and clinicopathologic characteristics of patients with PTC were analyzed, and the correlation between the presence of HT in PTC tissues and PD-L1 positive expression was studied.ResultsA total of 138 patients with PTC were included in this study, including 104 patients with PTC alone and 34 PTC patients with coexistent HT. The positive rate of PD-L1 expression in the 138 cases of PTC tissues was 35.5% (49/138), among which was 43.3% (45/104) in the pure PTC tissues, and 11.8% (4/34) in the PTC tissues with HT, the latter was significantly lower than the former (P=0.001). The results of univariate analysis showed that the positive rate of PD-L1 expression was related to the tumor size, the presence or absence of extraglandular invasion and HT in PTC patients (P<0.05), and the results of Spearman correlation analysis showed that the positive rate of PD-L1 expression was positively correlated with tumor size (rs=0.173, P=0.041) and extraglandular invasion (rs=0.197, P=0.021), and negatively correlated with whether TH was merged (rs=–0.284, P=0.001). The multivariate analysis results showed that the positive rate of PD-L1 expression was closely related to whether PTC with coexistent HT [OR=5.720, 95%CI (1.879, 17.411), P=0.002], and it was not found to be related to tumor size and presence of extraglandular invasion (P>0.05).ConclusionsPositive rate of PD-L1 expression has a certain relationship with tumor size and presence or absence of extraglandular invasion, and which in PTC patients with or without HT is significantly different, that is, positive rate of PD-L1 expression in PTC with HT is lower suggests that coexistent HT might be an inhibitory factor in occurrence of PTC, and immune microenvironment-related factors of PTC might be involved in occurrence and development of thyroid cancer.
ObjectiveTo understand the single-cell RNA sequencing (scRNA-seq) and its research progress in the tumor microenvironment (TME) of breast cancer, in order to provide new ideas and directions for the research and treatment of breast cancer. MethodThe development of scRNA-seq technology and its related research literature in breast cancer TME at home and abroad in recent years was reviewed. ResultsThe scRNA-seq was a quantum technology in high-throughput sequencing of mRNA at the cellular level, and had become a powerful tool for studying cellular heterogeneity when tissue samples were fewer. While capturing rare cell types, it was expected to accurately describe the complex structure of the TME of breast cancer. ConclusionsAfter decades of development, scRNA-seq has been widely used in tumor research. Breast cancer is a malignant tumor with high heterogeneity. The application of scRNA-seq in breast cancer research can better understand its tumor heterogeneity and TME, and then promote development of personalized diagnosis and treatment.
Lung cancer has a high morbidity and mortality, and invasion is one of the major factors that cause recurrence and death in lung cancer patients. Tumor-associated macrophages (TAMs) are cells that have the potential to secrete cytokines, growth hormones, inflammatory substrates, and protein hydrolases, which are associated with the growth, invasion and metastasis of tumors. In this article, we will explore the various chemicals that are manufactured to promote the invasion of lung cancer, as well as the numerous clinical therapeutic features that TAMs possess in the treatment of lung cancer. In addition, we look at the possibility that TAMs might be beneficial in the treatment of lung cancer. We have an innovative investigation of the huge variety of complex substances generated by TAMs, with the goal of determining whether or not the molecules under investigation have the potential to serve as new therapeutic targets. Throughout the whole of the presentation, a significant focus is placed on doing in-depth research to ascertain whether TAMs have the capability to reinforce as viable carriers for unique and creative medications. This not only provides novel concepts for the creation of new targeted therapies but also leads to the development of brand-new, cutting-edge methods for the manufacture of individualized medicines and drug carriers.
Objective To summarize the research progress on the regulation of hepatic sinusoidal microenvironment to promote liver regeneration based on liver sinusoidal endothelial cells (LSECs), aiming to further clarify the mechanism of liver regeneration and provide new ideas and methods for clinical promotion of liver regeneration and prevention of liver failure. Method The basic and clinical research studies on LSECs and liver regeneration at home and abroad in recent years were searched and reviewed. Results Differentiated LSECs played an important role in liver regeneration, regulated the homeostasis of hepatic sinusoid microenvironment by paracrine and autocrine, and participated in the whole process of promoting liver regeneration, such as hepatocyte proliferation and neovascularization after acute and chronic liver injury. Conclusion In the process of liver regeneration after all kinds of acute and chronic liver injury, LSECs promote liver regeneration by regulating hepatic sinusoid microenvironment, which will provide new strategies and methods for clinical promotion of liver regeneration and prevention of liver failure after hepatectomy.
Objective To introduce the inflammatory microenvironment and epithelial-mesenchymal transition process of hepatocellular carcinoma, and review the relationship between them. Methods Domestic and international literatures were collected to summary the relationship between epithelial-mesenchymal transition and the inflammatory microenvironment of hepatocellular carcinoma. Result Many inflammatory factors and viral gene encoding proteins in the inflammatory microenvironment play an important role in the process of epithelial-mesenchymal transition in hepatocellular carcinoma. Conclusions The inflammatory microenvironment of hepatocellular carcinoma is an indispensable role in the process of epithelial-mesenchymal transition. The inhibition and treatment of inflammatory microenvironment may play a more active role in the control of tumor invasion and metastasis.
One of the most important environmental cleanliness indicators is airborne microbe. However, the particularity of clean operating environment and controlled experimental environment often leads to the limitation of the airborne microbe research. This paper designed and implemented a microenvironment test chamber for airborne microbe research in normal test conditions. Numerical simulation by Fluent showed that airborne microbes were evenly dispersed in the upper part of test chamber, and had a bottom-up concentration growth distribution. According to the simulation results, the verification experiment was carried out by selecting 5 sampling points in different space positions in the test chamber. Experimental results showed that average particle concentrations of all sampling points reached 107 counts/m3 after 5 minutes’ distributing of Staphylococcus aureus, and all sampling points showed the accordant mapping of concentration distribution. The concentration of airborne microbe in the upper chamber was slightly higher than that in the middle chamber, and that was also slightly higher than that in the bottom chamber. It is consistent with the results of numerical simulation, and it proves that the system can be well used for airborne microbe research.
ObjectiveGelatin methacryloyl (GelMA)/hyaluronic acid methacryloyl (HAMA)/chitosan oligosaccharide (COS) hydrogel was used to construct islet biomimetic microenvironment, and to explore the improvement effect of GelMA/HAMA/COS on islet activity and function under hypoxia. Methods Islets cultured on the tissue culture plate was set as the control group, on the GelMA/HAMA/COS hydrogel with COS concentrations of 0, 1, 5, 10, and 20 mg/mL respectively as the experimental groups. Scanning electron microscopy was used to observe the microscopic morphology, rheometer test to evaluate the gel-forming properties, contact angle to detect the hydrophilicity, and the biocompatibility was evaluated by the scaffold extract to L929 cells [using cell counting kit 8 (CCK-8) assay]. The islets were extracted from the pancreas of 8-week-old Sprague Dawley rats and the islet purity and function were identified by dithizone staining and glucose-stimulated insulin secretion (GSIS) assays, respectively. Islets were cultured under hypoxia (1%O2) for 24, 48, and 72 hours, respectively. Calcein-acetyl methyl/propidium iodide (Calcein-AM/PI) staining was used to evaluate the effect of hypoxia on islet viability. Islets were cultured in GelMA/HAMA/COS hydrogels with different COS concentrations for 48 hours, and the reactive oxygen species kits were used to evaluate the antagonism of COS against islet reactive oxygen species production under normoxia (20%O2) and hypoxia (1%O2) conditions. Calcein-AM/PI staining was used to evaluate the effect of COS on islet activity under hypoxia (1%O2) conditions. Islets were cultured in tissue culture plates (group A), GelMA/HAMA hydrogels (group B), and GelMA/HAMA/COS hydrogels (group C) for 48 hours, respectively. Immunofluorescence and GSIS assays were used to evaluate the effect of COS on islet activity under hypoxia (1%O2) conditions, respectively. Results GelMA/HAMA/COS hydrogel had a porous structure, the rheometer test showed that it had good gel-forming properties, and the contact angle test showed good hydrophilicity. CCK-8 assay showed that the hydrogel in each group had good biocompatibility. The isolated rat islets were almost round, with high islet purity and insulin secretion ability. Islets were treated with hypoxia for 24, 48, and 72 hours, Calcein-AM/PI staining showed that the number of dead cells gradually increased with time, which were significantly higher than those in the non-hypoxia-treated group (P<0.001). Reactive oxygen staining showed that GelMA/HAMA/COS hydrogels with different COS concentrations could antagonize the production of reactive oxygen under normal oxygen and hypoxia conditions, and this ability was positively correlated with COS concentration. Calcein-AM/PI staining indicated that GelMA/HAMA/COS hydrogels with different COS concentrations could improve islet viability under hypoxia conditions, and cell viability was positively correlated with COS concentration. Immunofluorescence staining showed that GelMA/HAMA/COS hydrogel could promote the expression of islet function-related genes under hypoxia conditions. GSIS assay results showed that the insulin secretion of islets in hypoxia condition of group C was significantly higher than that of groups B and C (P<0.05). Conclusion GelMA/HAMA/COS hydrogel has good biocompatibility, promotes islet survival and function by inhibiting reactive oxygen species, and is an ideal carrier for building islet biomimetic microenvironment for islet culture and transplantation.
ObjectiveTo systematically summarize the research progress of multiparametric magnetic resonance imaging (mpMRI) in assessing tumor microenvironment (TME) heterogeneity in hepatocellular carcinoma (HCC), and to discuss its future development directions, limitations, and challenges. MethodsA comprehensive review was conducted to review domestic and international research progress on the use of mpMRI techniques in evaluating TME heterogeneity in HCC. ResultsmpMRI techniques can reflect TME heterogeneity features associated with postoperative recurrence in HCC from multiple perspectives, including cellular structure, function, substance metabolism, and neovascularization. These features encompass structural heterogeneity, cellular composition heterogeneity, and metabolic heterogeneity within the TME. mpMRI emerges as a potential tool for TME heterogeneity assessment, offering advantages such as non-invasiveness, absence of radiation exposure, and excellent reproducibility. However, the application of mpMRI in evaluating TME heterogeneity in HCC is still in its preliminary stages. Most studies have not conducted in-depth and systematic explorations of the specific pathological and biological mechanisms closely related to TME heterogeneity when utilizing mpMRI. This limitation significantly restricts the further clinical translation of relevant findings and necessitates further research for confirmation. ConclusionsmpMRI hold immense potential and promising application prospects in assessing TME heterogeneity in HCC, offering greater benefits for prognosis evaluation and individualized management of HCC patients. However, further exploration of the related pathological and biological mechanisms is essential to facilitate its clinical translation.
ObjectiveTo summarize the latest research progress and related mechanisms of cancer-associated fibroblasts (CAFs) in invasion, metastasis and drug resistance of breast cancer, so as to seek the best treatment strategy for patients with breast cancer metastasis and drug resistance. MethodThe literatures about CAFs research in breast cancer in recent years were searched and summarized. ResultsCAFs was the main stromal cell in tumor microenvironment (TME). By changing TME, the biological characteristics of CAFs could be changed and the growth and invasion of breast cancer cells could be induced. CAFs in breast cancer promotes the invasion and metastasis of breast cancer cells by interacting with inflammatory factors and promoting the formation of pre-transplantation ecosystems, and CAFs also mediates chemotherapy resistance to breast cancer, target resistance, endocrine resistance, and radiation resistance through the secretion of various cellular factors. ConclusionsAt present, some progress has been made in the research of CAFs in breast cancer, but there is still a certain gap to clinical application CAFs has a variety of functional phenotypes, so it is necessary to identify and characterize specific CAFs subtypes when studying new anti-CAFs therapeutic strategies. It has been proved that CAFs has great potential as a specific target for breast cancer treatment, but CAFs still lacks specific biomarkers. Therefore, an in-depth understanding of the biological characteristics and heterogeneity of CAFs can provide a reliable theoretical basis for developing drugs targeting CAFs.