In addition, let-7 miRNA participated in the regulation of cancer immunotherapy and modulated the biological functions of T cells in colorectal cancer microenvironment. Notably, previous study proved that the 3’UTR region of PD-L1 mRNA could be sponged by let-7 miRNA, and the expression levels of PD-L1 could be inhibited by overexpressing let-7 miRNA. Specifically, upregulated let-7 inhibited migration and invasion of NSCLC cells by synergistically targeting ITGB3 and MAP4K3. Among all the miRNAs, let-7 miRNA served as a tumor suppressor in multiple cancers, such as bladder cancer, ovarian cancer and NSCLC. For example, overexpression of miR-433 inhibited the development of NSCLC by targeting Smad2 and miR-421 played an oncogenic role in NSCLC progression. MicroRNAs (miRNAs) had widely been reported to regulate NSCLC progression. Previous data indicated that upregulation of PD-L1 promoted cancer cell growth and motility, and sustained stemness of breast cancer cells to facilitate drug resistance. Aside from regulating immune evasion of cancer cells, PD-L1 also directly regulated cancer cell functions and drug resistance. Mechanistically, cancer cells derived PD-L1 induced dysfunctions of CD8 + T cell contributed to immune evasion and disabled immune surveillance. Previous data indicated that cancer cells derived PD-L1 regulated the activity of CD8 + T cell activity, which was a pivotal component of the cellular immune response in tumor development. These therapeutic drugs included PD-1 inhibitors Nivolumab (Opdivo) as well as Pembrolizumab (Keytruda), and PD-L1 inhibitors Atezolizumab (Tecentriq), Durvalumab (Imfinzi) and Avelumab (Bavencio). Among those drugs and therapies, programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) blockade was proved to be novel cancer immunotherapies for cancers treatment, and the associated drugs were developed to treat NSCLC in clinic. Based on this, current cancer immunotherapies were developed to treat NSCLC in clinical practices. Tumor immune microenvironment was crucial for the development of non-small cell lung cancer (NSCLC), and NSCLC cells interacted with immune cells to facilitate immune evasion. Further results suggested that circ-CPA4 also positively regulated exosomal PD-L1, and the NSCLC cells with circ-CPA4 ablation re-activated CD8 + T cells in the co-culturing system. Notably, by co-culturing the NSCLC cells with CD8 + T cells isolated from human peripheral blood mononuclear cells (hPBMCs) in a transwell co-culturing system, we found that NSCLC cells inactivated CD8 + T cells in a secreted PD-L1-dependent manner. In addition, the NSCLC cells derived PD-L1-containing exosomes promoted cell stemness and increased resistance of NSCLC cells to cisplatin. Besides, knock-down of circ-CPA4 inhibited cell growth, mobility and epithelial-mesenchymal transition (EMT), and promoted cell death in NSCLC cells by downregulating PD-L1 through serving as a RNA sponge for let-7 miRNA. The Creative Commons Public Domain Dedication waiver ( ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.Ĭirc-CPA4 and PD-L1 were high-expressed, while let-7 miRNA was low-expressed in NSCLC cells and cancer tissues compared to the human bronchial epithelial (HBE) cells and their paired clinical normal adjacent tissues, respectively. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.
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