Immunotherapy has emerged as one of the most promising therapeutic strategies in cancer. The clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (CRISPR-Cas9) system, as an RNA-guided genome editing technology, is triggering a revolutionary change in cancer immunotherapy. With its versatility and ease of use, CRISPR-Cas9 can be implemented to fuel the production of therapeutic immune cells, such as construction of chimeric antigen receptor T (CAR-T) cells and programmed cell death protein 1 knockout. Therefore, CRISPR-Cas9 technology holds great promise in cancer immunotherapy. In this review, we will introduce the origin, development and mechanism of CRISPR-Cas9. Also, we will focus on its various applications in cancer immunotherapy, especially CAR-T cell-based immunotherapy, and discuss the potential challenges it faces.
Background: The role of interleukin family in colon cancer remained controversial. The purpose of this study was to investigate the association between interleukin family and colon cancer progression through bioinformatics methods and to validate such association in clinical patients. Methods: A total of 15 differentially expressed interleukins between the colon cancer tissue and normal colon tissue were evaluated from the Cancer Genome Atlas (TCGA) database with R software and only interleukin-7 (IL-7) was significantly associated with survival. The signaling pathway associated with IL-7 was then investigated using gene enrichment analysis. In addition, subsets of TNM were analyzed in detail and univariate and multivariate COX regression analysis were conducted. Finally, we performed western blotting, immunohistochemistry, cell proliferation and cell apoptosis analysis to examine the expression of IL-7 in patients with intestinal cancer. Results: The study demonstrated that IL-7 could inhibit the progression of colon cancer. In addition, IL-7 was found to be associated with overall survival (OS) and pathological stage. Further analysis of IL-7 expression with clinical data indicated that IL-7 was a key factor in inhibiting colon cancer progression. Conclusion: IL-7 was a key factor in inhibiting the progression of colon cancer and was closely related to overall survival.
Complement component C3, mainly synthesized by hepatocytes, acts as the convergence point of three different pathways in activating the complement cascade. Besides its well‐established roles in the extracellular milieu, C3 performs various intracellular functions such as immunomodulation and pathogen recognition. Although C3 is present at extremely high concentrations in hepatocytes, little is known about its intrahepatic function. In this study, we found that C3 knockout (C3−/−) mice displayed accelerated hepatic triglyceride (TG) accumulation compared with C57BL/6J wild type mice. Mechanistically, C3 deficiency impaired lipophagy in hepatocytes, owing to the disrupted interaction between C3 and autophagy‐related 16 like 1, which is essential for autolysosome assembly. Furthermore, lipophagy deficiency affected the function of the endoplasmic reticulum in C3−/− mice, subsequently affecting the expression of protein disulfide isomerase and activity of microsomal TG transfer protein, and ultimately impairing the production of hepatic very‐low‐density lipoproteins (VLDLs). Rapamycin and thapsigargin treatment accelerated VLDL secretion and alleviated hepatic lipid accumulation in C3−/− mice. Our study demonstrates that C3 promotes lipophagy to facilitate VLDL secretion in hepatocytes, thus playing an essential role in balancing TG levels in the liver.
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