Abstract 5247: Interleukin-11 could be a novel therapeutic target for lung adenocarcinoma patients

Abstract

Interleukin-11 (IL11) has been associated with tumorigenesis in a wide variety of tumors, including lung cancer, and it has been proposed as a diagnostic biomarker for lung adenocarcinoma. However, it is still not clear how IL11 affects the tumorigenesis. It is possible that, as other cytokines, it has a dual role in the tumor cell and tumoral microenvironment. Thus, the inhibition of IL11 could be an interesting therapeutic option to test in these patients. First, we confirmed the pro-tumorigenic effect of IL11 in patients and mouse models of lung adenocarcinoma (cancer cell lines xenografts, patient derived xenografts; PDXs and genetically engineered mouse models; GEMMs). Later, we knocked-down the expression of IL11 or its specific receptor IL11RA in adenocarcinoma cell lines in order to analyze their tumorigenic properties in vitro and in vivo. We confirmed that fibroblasts are a relevant source of IL11, so we knocked-down IL11 expression in order to analyze how it affects the fibroblasts´ properties, including the secretion of other pro-tumorigenic cytokines and growth factors. We reported that an increased expression of IL11 correlates with a poorer survival in lung adenocarcinoma patients and that IL11 stimulation increases the proliferation rates in xenografts, PDXs and GEMMs. On the contrary, IL11 or IL11RA knockdown in adenocarcinoma cell lines reduces their pro-tumorigenic properties in vitro and in vivo. Finally, the silencing of IL11 in fibroblasts reduces their proliferation, migration and secretion of pro-tumorigenic cytokines and growth factors. In conclusion, we propose that IL11 plays a direct pro-oncogenic role in lung adenocarcinoma tumoral cell and an indirect role in tumoral microenvironment. The genetic ablation of IL11 has an anti-tumoral effect, so it could be interesting to develop a pharmacological tool which neutralizes the IL11-IL11RA signaling to test as a therapeutic strategy in preclinical models. Thus, IL11 could represent a potential therapeutic target that deserves to be more exhaustively studied in the clinical settings. Citation Format: Laura Ojeda, Cristina Cirauqui, Sonia Molina-Pinelo, Eva M Garrido-Martín, Javier Ramos-Paradas, Patricia Yagüe, Alba Santos, Nuria Carrizo, Ana B. Enguita, Maria Teresa Muñoz, Jose Luis Solorzano, Luis Paz-Ares, Irene Ferrer. Interleukin-11 could be a novel therapeutic target for lung adenocarcinoma patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5247.