Novel therapy for pancreatic cancer combined IFNA-STAT3 inhibition with imuno checkpoint blocker

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20790
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Tohoku University
• Principal Investigator: Inoue Koetsu 東北大学, 医学系研究科, 大学院非常勤講師 (30912711)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: 膵癌 / 癌微小環境 / 腫瘍免疫

Outline of Final Research Achievements

Pancreatic cancer is immune suppressive tumor. In this study, we evaluated if IFNA-STAT3 suppression can enhance tumor immunity with mouse model. We employed IFNAR1 inhibition to block INFA-STAT3. We found that genetic IFNAR1 inhibition could enhance immunotherapy. Next, we employed anti-IFNAR1 antibody to regulate the IFNA-STAT3 axis. As well as genetic inhibition, anti-IFNAR1 antibody enhanced the effect of ICB. To this end, we evaluated the STAT3 activation in tumor tissue. By blocking IFNA signaling , we confirmed that STS3 was suppressed with western blotting.

Free Research Field

膵癌

Academic Significance and Societal Importance of the Research Achievements

本実験で、免疫治療の効果が乏しい膵癌において、新たな治療の発見につながる結果が得られた。IFNAシグナル遮断が腫瘍免疫を活性化させるという概念は新しく、膵癌のみでなく、他の癌腫にも応用できる可能性がある。IFNA-STAT3の遮断はがん細胞の腫瘍増殖を抑制させる上、さらにICBの効果が上乗せできるので、治療効果が極めて高いと考えられる。今回、IFNgが腫瘍組織内で上昇していることが判明し、IFNgを介した、腫瘍免疫の賦活化が想定される。今後、メカニズムの解明を続け、臨床試験に繋げていきたいと考えている。