Pancreatic cancer is one of malignant diseases with poor prognosis. Despite the recent progress for preoperative neoadjuvant chemoradiotherapy, the long term prognosis is still poor to make forward new treatment strategy. We have recently reported novel mechanism of anticancer reagents to impact patients' prognosis improving tumor microenvironment other than its direct cytotoxic effects (Ann Surg Oncol 2013, Cancer Sci 2014). The underlying mechanism include inhibition of HLA class I down regulation and Treg infiltration, increase of CD4 and CD8 T cell infiltration (Int J Clin Oncol 2015, Cancer Res 2015). Here we report that GM-CSF production was significantly enhanced in various PDAC cell lines after treatment with chemotherapy including gemcitabine or 5-FU, which induced the differentiation of CD14 positive monocytes into myeloid-derived suppressor cells (MDSC). This differentiation was promoted through MAPK signal pathway or NFkB pathway. Furthermore, blockade of GM-CSF with monoclonal antibodies helped to restore T-cell proliferation when co-cultured with monocytes stimulated with tumor supernatants. GM-CSF expression was also observed in primary tumors and correlated with poor prognosis in 68 PDAC patients analyzed by immunohistochemistry. We expect that postoperative prognosis of pancreatic cancer would be more improved by multidisciplinary strategy targeting MDSC and GM-CSF followed by curative surgical intervention.
Citation Format: Takahiro Tsuchikawa, Shintaro Takeuchi, Toru Nakamura, Mizuna Takahashi, kazuho Inoko, Toshihiro Kushibiki, Koji Hontani, Masato Ono, Shota Kuwabara, Toshiaki Shichinohe, Satoshi Hirano. Novel immunotherapy for intractable pancreatic cancer focusing on the myeloid derived suppressor cells in the tumor microenvironment [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A135.