Cytokine & Growth Factor Reviews最新文献

Chemoresistance constitute a major obstacle in cancer treatment, leading to limited options and decreased patient survival. Recent studies have revealed a novel mechanism of chemoresistance acquisition: the transfer of information via exosomes, small vesicles secreted by various cells. Exosomes play a crucial role in intercellular communication by carrying proteins, nucleic acids, and metabolites, influencing cancer cell behavior and response to treatment. One crucial mechanism of resistance is cancer metabolic reprogramming, which involves alterations in the cellular metabolic pathways to support the survival and proliferation of drug-resistant cancer cells. This metabolic reprogramming often includes increased glycolysis, providing cancer cells with the necessary energy and building blocks to evade the effects of chemotherapy. Notably, exosomes have been found to transport glycolytic enzymes, as identified in proteomic profiling, leading to the reprogramming of metabolic pathways, facilitating altered glucose metabolism and increased lactate production. As a result, they profoundly impact the tumor microenvironment, promoting tumor progression, survival, immune evasion, and drug resistance.Understanding the complexities of such exosome-mediated cell-to-cell communication might open new therapeutic avenues and facilitate biomarker development in managing cancers characterized by aggressive glycolytic features. Moreover, given the intricate nature of metabolic abnormalities combining future exosome-based-targeted therapies with existing treatments like chemotherapy, immunotherapy, and targeted therapies holds promise for achieving synergistic effects to overcome resistance and improve cancer treatment outcomes.

In the tumor microenvironment (TME), exosomes secreted by cells form interactive networks between the tumor cells and immune cells, thereby regulating immune signaling cascades in the TME. As key messengers of cell-to-cell communication in the TME, exosomes not only take charge of tumor cell antigen presentation to the immune cells, but also regulate the activities of immune cells, inhibit immune function, and, especially, promote immune resistance, all of which affects the therapeutic outcomes of tumors. Exosomes, which are small-sized vesicles, possess some remarkable advantages, including strong biological activity, a lack of immunogenicity and toxicity, and a strong targeting ability. Based on these characteristics, research on exosomes as biomarkers or carriers of tumor therapeutic drugs has become a research hotspot in related fields. This review describes the role of exosomes in cell communications in the TME, summarizes the effectiveness of exosome-based immunotherapy in overcoming immune resistance in cancer treatment, and systematically summarizes and discusses the characteristics of exosomes from different cell sources. Furthermore, the prospects and challenges of exosome-related therapies are discussed.

Pancreatic cancer is characterized by its high malignancy, insidious onset and poor prognosis. Most patients with pancreatic cancer are usually diagnosed at advanced stage or with the distant metastasis due to the lack of an effective early screening method. Liquid biopsy technology is promising in studying the occurrence, progression, and early metastasis of pancreatic cancer. In particular, exosomes are pivotal biomarkers in lipid metabolism and liquid biopsy of blood exosomes is valuable for the evaluation of pancreatic cancer. Lipid metabolism is crucial for the formation and activity of exosomes in the extracellular environment. Exosomes and lipids have a complex relationship of mutual influence. Furthermore, spatial metabolomics can quantify the levels and spatial locations of individual metabolites in cancer tissue, cancer stroma, and para-cancerous tissue in pancreatic cancer. However, the relationship among exosomes, lipid metabolism, and pancreatic cancer is also worth considering. This study mainly updates the research progress of metabolomics in pancreatic cancer, their relationship with exosomes, an important part of liquid biopsy, and their lipometabolic roles in pancreatic cancer. We also discuss the mechanisms by which possible metabolites, especially lipid metabolites through exosome transport and other processes, contribute to the recurrence and metastasis of pancreatic cancer.

The term small extracellular vesicle (sEV) is a comprehensive term that includes any type of cell-derived, membrane-delimited particle that has a diameter < 200 nm, and which includes exosomes and smaller microvesicles. sEVs transfer bioactive molecules between cells and are crucial for cellular homeostasis and particularly during tumor development, where sEVs provide important contributions to the formation of the premetastic niche and to their altered metabolism. sEVs are thus legitimate targets for intervention and have also gained increasing interest as an easily accessible source of biomarkers because they can be rapidly isolated from serum/plasma and their molecular cargo provides information on their cell-of origin. To target sEVs that are specific for a given cell/disease it is essential to identify EV surface proteins that are characteristic of that cell/disease. Mass-spectrometry based proteomics is widely used for the identification and quantification of sEV proteins. The methods used for isolating the sEVs, preparing the sEV sample for proteomics analysis, and mass spectrometry analysis, can have a strong influence on the results and requires careful consideration. This review provides an overview of the approaches used for sEV proteomics and discusses the inherent compromises regarding EV purity versus depth of coverage. Additionally, it discusses the practical applications of the methods to unravel the involvement of sEVs in regulating the metabolism of pancreatic ductal adenocarcinoma (PDAC). The metabolic reprogramming in PDAC includes enhanced glycolysis, elevated glutamine metabolism, alterations in lipid metabolism, mitochondrial dysfunction and hypoxia, all of which are crucial in promoting tumor cell growth. A thorough understanding of these metabolic adaptations is imperative for the development of targeted therapies to exploit PDAC's vulnerabilities.

Esophageal carcinoma is among the most fatal malignancies with increasing incidence globally. Tumor onset and progression can be driven by metabolic reprogramming, especially during esophageal carcinoma development. Exosomes, a subset of extracellular vesicles, display an average size of ∼100 nanometers, containing multifarious components (nucleic acids, proteins, lipids, etc.). An increasing number of studies have shown that exosomes are capable of transferring molecules with biological functions into recipient cells, which play crucial roles in esophageal carcinoma progression and tumor microenvironment that is a highly heterogeneous ecosystem through rewriting the metabolic processes in tumor cells and environmental stromal cells. The review introduces the reprogramming of glucose, lipid, amino acid, mitochondrial metabolism in esophageal carcinoma, and summarize current pharmaceutical agents targeting such aberrant metabolism rewiring. We also comprehensively overview the biogenesis and release of exosomes, and recent advances of exosomal cargoes and functions in esophageal carcinoma and their promising clinical application. Moreover, we discuss how exosomes trigger tumor growth, metastasis, drug resistance, and immunosuppression as well as tumor microenvironment remodeling through focusing on their capacity to transfer materials between cells or between cells and tissues and modulate metabolic reprogramming, thus providing a theoretical reference for the design potential pharmaceutical agents targeting these mechanisms. Altogether, our review attempts to fully understand the significance of exosome-based metabolic rewriting in esophageal carcinoma progression and remodeling of the tumor microenvironment, bringing novel insights into the prevention and treatment of esophageal carcinoma in the future.

The hallmark of chronic inflammatory diseases is immune evasion. Successful immune evasion involves numerous mechanisms to suppress both adaptive and innate immune responses. Either direct contact between cells or paracrine signaling triggers these responses. Exosomes are critical drivers of these interactions and exhibit both immunogenic and immune evasion properties during the development and progression of various chronic inflammatory diseases. Exosomes carry diverse molecular cargo, including lipids, proteins, and RNAs that are crucial for immunomodulation. Moreover, recent studies have revealed that exosomes and their cargo-loaded molecules are extensively involved in lipid remodeling and metabolism during immune surveillance and disease. Many studies have also shown the involvement of lipids in controlling immune cell activities and their crucial upstream functions in regulating inflammasome activation, suggesting that any perturbation in lipid metabolism results in abnormal immune responses. Strikingly, the expanded immunometabolic reprogramming capacities of exosomes and their contents provided insights into the novel mechanisms behind the prophylaxis of inflammatory diseases. By summarizing the tremendous therapeutic potential of exosomes, this review emphasizes the role of exosome-derived noncoding RNAs in regulating immune responses through the modulation of lipid metabolism and their promising therapeutic applications.

Neoplasms are one of the most concerned public health problems worldwide. Digestive system neoplasms, with a high morbidity and mortality, is one of the most common malignant tumors in human being. It is found that exosomes act as an intercellular communication media to carry the metabolic and genetic information of parental cells to target cells. Likely, exosomes participate in lipid metabolism and regulates multiple processes in digestive system neoplasms, including the information transmission among cancer cells, the formation of neoplastic microenvironment, and the neoplastic biological behaviors like metastasis, invasion, and the chemotherapy resistance. In this review, we firstly introduce the main mechanisms whereas exosomes act as intercellular lipometabolic communication mediator in digestive system neoplasms. Thereafter we introduce the relationship between exosomes lipid metabolism and various type of digestive system neoplasms, including gastric cancer, hepatocellular carcinoma, pancreatic cancer, and colorectal cancer. Eventually, we summarized and prospected the development and implication of exosomes in digestive system neoplasms. The further research of exosomes as intercellular lipid metabolism mediator will contribute to accurate and efficient diagnosis and treatment of digestive system neoplasms.

Increasing evidence highlights the role of lipid metabolism in tumorigenesis and tumor progression. Targeting the processes of lipid metabolism, including lipogenesis, lipid uptake, fatty acid oxidation, and lipolysis, is an optimal strategy for anti-cancer therapy. Beyond cell-cell membrane surface interaction, exosomes are pivotal factors that transduce intercellular signals in the tumor microenvironment (TME). Most research focuses on the role of lipid metabolism in regulating exosome biogenesis and extracellular matrix (ECM) remodeling. The mechanisms of exosome and ECM-mediated reprogramming of lipid metabolism are currently unclear. We summarize several mechanisms associated with the regulation of lipid metabolism in cancer, including transport of exosomal carriers and membrane receptors, activation of the PI3K pathway, ECM ligand-receptor interactions, and mechanical stimulation. This review aims to highlight the significance of these intercellular factors in TME and to deepen the understanding of the functions of exosomes and ECM in the regulation of lipid metabolism.

Inflammatory bowel disease (IBD), as a representative inflammatory disease, currently has multiple effective treatment options available and new therapeutic strategies are being actively explored to further increase the treatment options for patients with IBD. Furthermore, biologic agents and small molecule drugs developed for ulcerative colitis (UC) and Crohn's disease (CD) have evolved toward fewer side effects and more accurate targeting. Novel inhibitors that target cytokines (such as IL-12/23 inhibitors, PDE4 inhibitors), integrins (such as integrin inhibitors), cytokine signaling pathways (such as JAK inhibitors, SMAD7 blocker) and cell signaling receptors (such as S1P receptor modulator) have become the preferred treatment choice for many IBD patients. Conventional therapies such as 5-aminosalicylic acid, corticosteroids, immunomodulators and anti-tumor necrosis factor agents continue to demonstrate therapeutic efficacy, particularly in combination with drug therapy. This review integrates research from chemical, biological and adjuvant therapies to evaluate current and future IBD therapies, highlighting the mechanism of action of each therapy and emphasizing the potential of development prospects.