Abstract B23: CD4+ T lymphocytes promote pancreatic cancer progression by suppressing anti-tumor immune responses

Abstract

Abstract Pancreatic cancer, one of the deadliest human malignancies, is associated with oncogenic Kras and is most commonly preceded by precursor lesions known as Pancreatic Intraepithelial Neoplasias (PanINs). PanIN formation is accompanied by the establishment of an immune-tolerant microenvironment. However, the immune contribution to the initiation of pancreatic cancer is currently poorly understood. Here, we show that oncogenic Kras-expressing epithelial cells drive the establishment of an immunosuppressive microenvironment through the recruitment and activity of CD4+ T cells. We further show that CD4+ T cells functionally repress the activity of CD8+ T cells. Elimination of CD4+ T cells uncovers CD8+ T cells anti-neoplastic function, and blocks the onset of pancreatic carcinogenesis. Thus, our studies uncover essential and opposing roles of immune cells during PanIN formation, and provide rationale to explore immune-modulatory approaches in pancreatic cancer. Citation Format: Yaqing Zhang, Wei Yan, Wei Yan, Esha Mathew, Filip Bednar, Shanshan Wan, Meredith A. Collins, Rebecca A. Evans, Theodore H. Welling, Robert H. Vonderheide, Marina Pasca di Magliano, Marina Pasca di Magliano. CD4+ T lymphocytes promote pancreatic cancer progression by suppressing anti-tumor immune responses. [abstract]. In: Proceedings of the AACR Special Conference on RAS Oncogenes: From Biology to Therapy; Feb 24-27, 2014; Lake Buena Vista, FL. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(12 Suppl):Abstract nr B23. doi: 10.1158/1557-3125.RASONC14-B23