Abstract A02: Stat3 plays a critical role in the establishment of immunosuppressive tumor microenvironment: Implications for tumor immunsurviellance and metastatic progression

Immune surveillance is thought to play a critical role in promoting the elimination of developing malignant lesions through activation of immune response. However, cancer cells eventually acquire the ability to escape immune surveillance by favoring recruitment of immune cell types that exert an inflammatory and immunosuppressive state. Despite the importance of immune surveillance, the molecular mechanisms that promote escape from immune remains poorly defined. Here we demonstrate that expression of the Stat3 transcription factor in the tumor epithelial is involved in promoting an immunosuppressive tumor microenvironment. To investigate the role of Stat3 in modulating the tumor immune-microenvironment, we ablated Stat3 in the tumor epithelia of an inducible PyV mT model of mammary tumor progression. Molecular and pathological analyses of tumor progression revealed that Stat3 deficient tumors were initially able to form hyperplastic and early adenoma–like lesions with no obvious impact on the proliferative or apoptotic status on these epithelial lesions. However, these early premalignant lesions completely regressed, thereby preventing the emergence of mammary tumors in the majority of animals. Tumor regression was correlated with a massive infiltration of T lymphocytes and F4/80 positive macrophages into Stat3 deficient lesions. However focal Stat3 deficient mammary tumors escaped immune surveillance after a long latency period in a minority of the affected animals. Our data argue that tumor epithelial expression of Stat3 plays a critical role in promoting an immune suppressive tumor microenvironment . Note: This abstract was not presented at the conference. Citation Format: Laura M. Jones, Miranda Broz, Jill Ranger, Josie Ursini-Siegel, Matthew Krummel, William J. Muller. Stat3 plays a critical role in the establishment of immunosuppressive tumor microenvironment: Implications for tumor immunsurviellance and metastatic progression. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr A02.