Low-dose gemcitabine induces major histocompatibility complex class I-related chain A/B expression and enhances an antitumor innate immune response in pancreatic cancer.

2015 Fiscal Year Final Research Report

• Project/Area Number: 25462106
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kanazawa University
• Principal Investigator: Ohta Tetsuo 金沢大学, 医学系, 教授 (40194170)
• Co-Investigator(Kenkyū-buntansha): Miyashita Tomoharu 金沢大学, 医学系, 助教 (30397210)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 膵癌 / 術前化学療法 / 免疫逃避機構 / MICA/B / Gemcitabine / Valpronic acid / 自然免疫機構

Outline of Final Research Achievements

We investigated the effect of gemcitabine (GEM), a key drug for pancreatic cancer treatment, on the expression of cell surface MICA/B in pancreatic cancer cells and resulting cytotoxicity of γδ T cells. MICA and CD16 expressions from resected pancreatic cancer patient specimens, which received neoadjuvant chemotherapy (NAC) with GEM, were analyzed by immunohistochemistry. Immunohistochemical staining demonstrated that MICA expression in tumor cells and CD16 positive cells surrounding tumors were significantly higher in the NAC group compared to that of the control group. The present results indicate that low-dose GEM-induced MICA/B expression enhances innate immune function rather than cytotoxicity in pancreatic cancer. In addition, our result suggests that the inhibition of cleavage and release of MIC molecules from the tumor surface could potentially improve NKG2D-dependent cytotoxicity.

Free Research Field

肝胆膵外科