Augmentation of anti-tumor effect by less invasive hyperthermia

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10548
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Osaka University
• Principal Investigator: Takeda Tsutomu 大阪大学, 医学系研究科, 招へい教授 (80236471)
• Co-Investigator(Kenkyū-buntansha): 山本 浩文 大阪大学, 医学系研究科, 教授 (30322184) ; 長谷川 武夫 大阪大学, 医学系研究科, 招へい教授 (80077784)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 温熱療法 / 免疫チェックポイント阻害剤 / PD-L1

Outline of Final Research Achievements

Under the hyperthermia therapy, the immune checkpoint system is largely unknown. Immunohistochemical studies using clinical samples of colon and breast cancer indicated that hyperthermia treatment induced PD-L1 expression and MHC class I, and that the number of CD8+ T cell increased around the tumor cells. Because CD8+ T cell can release IFN-γ, we examined by western blot analysis and found that exposure of IFN-γ on the MC38 mouse colon cancer cells led to increase in p-STAT1 and IRF1 expression as well as PD-L1 induction. Hyperthermal therapy using MC38 tumor-bearing mouse model led to necrosis in the tumors, facilitated CD8+ T cell invasion, but simultaneously enhanced expression of PD-L1 and its related molecules. Finally, we could observe that the combination therapy of hyperthermia and the anti PD-L1 antibody led to the more effective effect. In conclusion, combination therapy of hyperthermia and the immune checkpoint inhibitor may be an efficient anti-tumor treatment.

Free Research Field

化学療法、温熱療法、癌治療

Academic Significance and Societal Importance of the Research Achievements

温熱療法は主として症状緩和に利用され、単独では癌の治療効果は乏しいが、抗癌剤や放射線の増強効果が知られている。近年、免疫チェックポイント阻害剤が新たな癌治療として脚光を浴びているが、本研究では温熱療法と免疫治療との併用効果をもたらすメカニズムが示唆された。動物実験の数を増やした検証が必要であるが基幹となるセオリーを示せたことは大きな意義があり、今後の温熱免疫療法の基盤となる研究であると考える。