Study of the impact of the IL-7R on non-small cell lung cancer

• Autor(a) principal: Rosado, Pedro Lino
• Data de Publicação: 2023
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10362/162289
• topic: Non-small cell lung cancer (NSCLC); Interleukin-7 (IL-7); Thymic stromal lymphopoietin (TSLP); Survival; Migration; Invasion; Ciências Médicas

Abstract Lung cancer, a complex and multifaceted disease, is the second most common malignancy and the leading cause of cancer related deaths worldwide. Non-small cell lung cancer (NSCLC) comprises most lung cancer cases, and, despite advances in diagnostic and therapeutic regimens, it remains a global health burden mainly due to diagnosis at advanced stages and treatment resistance. Interleukin-7 (IL-7) and thymic stromal lymphopoietin (TSLP) are cytokines that due to their roles in regulating immune responses and tumour-promoting functions have been gathering attention and been studied in the context of tumorigenesis. IL-7 plays a pivotal role in the proliferation and differentiation of immune players including T-cells and B-cells. In addition to its role in lymphopoiesis, IL-7 is closely related with tumorigenesis reportedly increasing the viability and proliferation of several tumours, haematological and non-haematological, including NSCLC. TSLP, recognized for its role in allergies and lung inflammation, has recently emerged as a significant mediator of tumorigenesis, either dependently or independently of type 2 immune responses. Nevertheless, a clear role of IL-7 or TSLP in NSCLC remains to be established. The work presented and discussed herein sought to clarify the role of the IL-7, and TSLP signalling axis in NSCLC. We found that NSCLC cells can express the IL-7Rα, the TSLPR, and both IL-7 and TSLP, at different extents. By stimulating with IL-7, we observed no activation of the signalling pathway nor changes in survival, likely due to the absence of expression of the gamma chain observed, which is necessary for IL-7-mediated signalling. On the contrary, TSLP stimulation led to the activation of its corresponding signalling pathway in NSCLC cell line H1975. Importantly, we observed several mechanisms by which TSLP might promote tumorigenesis. TSLP stimulation impacted lung cancer cell migration and invasion, and augmented cell viability. Overall, our work suggests that TSLP may play an important role in NSCLC development and progression and its inhibition may have a therapeutic value. As for IL-7 no relevant link was found, but further studies need to be performed to dissect its tumorigenic potential in the context of lung cancer.