The therapeutic potential of exosomes in immunotherapy.

Exosomes are found in various tissues of the body and carry abundant contents including nucleic acids, proteins, and metabolites, which continuously flow between cells of various tissues and mediate important intercellular communication. In addition, exosomes from different cellular sources possess different physiopathological immunomodulatory effects, which are closely related to the immune regeneration of normal or abnormal organs and tissues. Here, we focus on the mechanistic interactions between exosomes and the human immune system, introduce the immuno-regenerative therapeutic potential of exosomes in common clinical immune-related diseases, such as infectious diseases, autoimmune diseases, and tumors, and reveal the safety and efficacy of exosomes as a novel cell-free immune regenerative therapy.

Small extracellular vesicles purification and scale-up.

Exosomes are small extracellular vesicles (sEVs) secreted by cells. With advances in the study of sEVs, they have shown great potential in the diagnosis and treatment of disease. However, sEV therapy usually requires a certain dose and purity of sEVs to achieve the therapeutic effect, but the existing sEV purification technology exists in the form of low yield, low purity, time-consuming, complex operation and many other problems, which greatly limits the application of sEVs. Therefore, how to obtain high-purity and high-quality sEVs quickly and efficiently, and make them realize large-scale production is a major problem in current sEV research. This paper discusses how to improve the purity and yield of sEVs from the whole production process of sEVs, including the upstream cell line selection and cell culture process, to the downstream isolation and purification, quality testing and the final storage technology.

Exosomes derived from cancer cells relieve inflammatory bowel disease in mice.

Exosome therapy has garnered significant attention due to its natural delivery capabilities, low toxicity, high biocompatibility, and potential for personalised treatment through engineering modifications. Recent studies have highlighted the ability of tumour cell-derived exosomes (TDEs) to interact with immune cells or modify the immune microenvironment to suppress host immune responses, as well as their unique homing ability to parental cells. The core question of this study is whether this immunomodulatory property of TDEs can be utilised for the immunotherapy of inflammatory diseases. In our experiments, we prepared exosomes derived from murine colon cancer cells CT26 (CT26 exo) using ultracentrifugation, characterised them, and conducted proteomic analysis. The therapeutic potential of CT26 exo was evaluated in our dextran sulphate sodium salt (DSS)-induced inflammatory bowel disease (IBD) mouse model. Compared to the control and 293 T exo treatment groups, mice treated with CT26 exo showed a reduction in the disease activity index (DAI) and colon shortening rate, with no noticeable weight loss. Haematoxylin and eosin (H&E) staining of colon paraffin sections revealed reduced inflammatory infiltration and increased epithelial goblet cells in the colons of CT26 exo-treated group. Furthermore, we conducted preliminary mechanistic explorations by examining the phenotyping and function of CD4+ T cells and dendritic cells (DCs) in the colonic lamina propria of mice. The results indicated that the ameliorative effect of CT26 exosomes might be due to their inhibition of pro-inflammatory cytokine secretion by colonic DCs and selective suppression of Th17 cell differentiation in the colon. Additionally, CT26 exo exhibited good biosafety. Our findings propose a novel exosome-based therapeutic approach for IBD and suggest the potential application of TDEs in the treatment of inflammatory diseases.

[Analysis of Clinicopathologic Features of 9 Cases of 
SMARCA4-deficient Non-small Cell Lung Cancer].

BACKGROUND: SMARCA4-deficient non-small cell lung cancer (SMARCA4-dNSCLC) is a rare primary lung malignancy. These diseases are not listed separately in the 2021 World Health Organization (WHO) classification of lung neoplasms, but they have special morphological, immunophenotypic and molecular genetic characteristics. This study aims to improve understanding of SMARCA4-dNSCLC by discussing the clinicopathological features, diagonosis and differential diagnosis of the disease. METHODS: The clinical and imaging data of 9 cases of SMARCA4-dNSCLC diagnosed in Shanghai Changhai Hospital from January 2020 to March 2022 were collected. The clinicopathological features were analyzed by histological and immunohistochemical staining, and the literature was reviewed. RESULTS: The median age of 9 patients was 65 years old. Six men were smokers. The average maximum diameter of tumor was 3.3 cm. Six cases had been metastasized. The imaging showed that it was an infiltrating mass with unclear boundary and 3 cases invaded the pleura. Nine cases were diagnosed as SMARCA4-dNSCLC, which mainly showed three pathological forms including classic lung adenocarcinoma, mucinous adenocarcinoma and poorly differentiated carcinoma. Poorly differentiated tumor cells are epithelioid, syncytial or rhabdomyoid, the cytoplasm was rich, the cytoplasm could be completely transparent to eosinophilic, eosinophilic globules or small abscesses could be seen, showing solid flakes, with more inflammatory cells and flake necrosis in the stroma. Immunohistochemistry showed that SMARCA4 was negative in all cases and eight cases demonstrated cytokeratin 5.2 (CAM5.2) and cytokeratin 7 (CK7) was diffusely strongly positive, p40 was negative, thyroid transcription factor-1 (TTF-1) was negative in 6 cases, partially positive in 2 cases and diffusely positive in 1 case. CONCLUSIONS: SMARCA4-dNSCLC is a rare subtype of lung cancer with complex and diverse pathological morphology. The characteristic of immunohistochemical phenotype can assist in the diagnosis.