Panoply™ Human IL17A Knockdown Stable Cell Line

The tumor microenvironment plays a pivotal role in the initiation and progression of non-small cell lung cancer (NSCLC) and influences the efficacy of immunotherapy. The pro-inflammatory cytokine interleukin-17A (IL-17A) mediates critical immune responses within the tumor microenvironment. Here, researchers investigated the potential role of IL-17A in NSCLC and the underlying mechanisms. The study found that IL-17A is widely expressed in NSCLC tumor tissues and positively correlates with PD-L1 expression. In vitro experiments demonstrated that IL-17A promotes the migration, invasion, and colony-forming ability of lung cancer cells. Furthermore, IL-17A upregulated the expression of N-cadherin, Twist, and Snail while downregulating E-cadherin in NSCLC cells; in T-cell-mediated killing assays, IL-17A enhanced cell survival. Mechanistic studies revealed that IL-17A induces the production of reactive oxygen species (ROS) and upregulates Nrf2 and p62 expression, thereby inhibiting autophagy and reducing PD-L1 degradation. In vivo experiments showed that treatment with an anti-IL-17A monoclonal antibody alone delayed subcutaneous tumor growth in mice; however, when combined with an anti-PD-L1 monoclonal antibody, PD-L1 expression in tumor tissues decreased, and the therapeutic efficacy was attenuated. These findings indicate that IL-17A promotes NSCLC progression and inhibits autophagy via the ROS/Nrf2/p62 pathway, leading to increased PD-L1 expression in cancer cells. Modulating IL-17A may influence the efficacy of immunotherapy.

IL-17A is highly expressed in non-small cell lung cancer (NSCLC) cells. To investigate its impact on tumor cells, researchers generated A549 and SPC-A-1 lung adenocarcinoma cell lines with either IL-17A knockdown or IL-17A overexpression. Wound healing assays demonstrated that IL-17A-overexpressing A549 and SPC-A-1 cells exhibited significantly enhanced wound healing capabilities, whereas IL-17A-knockdown cells showed significantly reduced capabilities (Figure 1A). Transwell assays further revealed a significant increase in the number of migrating cells in the IL-17A-overexpression group compared to the control group, while the migratory capacity of IL-17A-knockdown cells was diminished. Additionally, cells overexpressing IL-17A demonstrated an increased ability to degrade the extracellular matrix and penetrate to the lower chamber of the Transwell insert; in contrast, IL-17A-knockdown cells showed a significantly reduced capacity to degrade the extracellular matrix (Figure 1B). Colony formation assays showed that A549 and SPC-A-1 cells with high IL-17A expression exhibited significantly enhanced colony-forming ability, suggesting that IL-17A promotes tumor cell proliferation (Figure 1C). These results indicate that IL-17A promotes the proliferation, migration, and invasion of NSCLC cells. Furthermore, the expression levels of epithelial-mesenchymal transition (EMT)-related markers-N-cadherin, Snail, and Twist-were significantly elevated in IL-17A-overexpressing cells, whereas E-cadherin protein levels were significantly increased in IL-17A-knockdown cells (Figure 1D). Researchers also assessed E-cadherin expression using immunofluorescence, confirming a negative correlation between IL-17A and E-cadherin expression (Figure 1E). In summary, IL-17A promotes NSCLC cell proliferation, migration, invasion, and EMT, all of which may accelerate tumor progression.

Figure 1. IL-17A could promote NSCLC cell proliferation, migration, invasion and EMT. (Liao H, et al., 2023)