The role of STAT3 (signal transducer and activator of transcription 3) in non-small cell lung cancer (NSCLC)

• Published in: The Journal of immunology (1950) 2016-05, Vol.196 (1_Supplement), p.73-73.17
• Main Authors: Heim, Lisanne, Andreev, Katerina, Balabko, Ljubov, Trufa, Denis Iulian, Sirbu, Horia, Hartmann, Arndt, Finotto, Susetta
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.196.Supp.73.17

Non-small cell lung cancer (NSCLC) is associated with high mortality worldwide underlining the need for novel therapeutic approaches. Signal transducer and activator of transcription 3 (STAT3) is activated via pro-inflammatory cytokines and growth factors (e.g. IL-6, EGF, VEGF) and may promote tumorigenesis by regulating cellular senescence, proliferation and apoptosis. We recently found an upregulation of the IL-6R expression in the tumoral region of patients with lung adenocarcinoma (ADC) as compared to the tumoral region of patients with squamous cell lung carcinoma (SCC). Consistently, increased levels of pSTAT3 were observed in the tumoral region of ADC as compared to SCC patients. Moreover, stimulation of A549 lung adenocarcinoma cells with IL-6 activates pSTAT3 and promotes cell proliferation. STAT3 is also important for the differentiation of both Foxp3+ T regulatory cells which suppress the anti-tumor immune response and RORγt+ T helper 17 cells, a T cell subtype expanded in lung adenocarcinoma. Indeed, ablation of STAT3 in hematopoietic cells triggers an intrinsic immune-surveillance system that inhibits tumor growth and metastasis. However, the role of STAT3 in tumor-infiltrating lymphocytes (TIL) in NSCLC is largely unknown. We therefore will investigate the functional effects of STAT3 inactivation in T cells in a murine model of lung adenocarcinoma by using mice with conditional inactivation of STAT3 (STAT3fl/flCD4Cre). To detect STAT3-regulated genes we will isolate TIL of tumor-bearing STAT3 conditional knockout mice and control littermates. These studies will provide new insights into the functional role of STAT3 in NSCLC and may lead to novel immunotherapeutic approaches for this disease.