Analysis of molecular mechanisms underlying acquired resistance of tumor cells responding to anti-tumor immunity

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02695
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Juntendo University
• Principal Investigator: TAKEDA KAZUYOSHI 順天堂大学, 医学(系)研究科(研究院), 准教授 (80272821)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 抗腫瘍免疫 / 免疫抵抗性 / CD155 / TRAIL/DR5 / Importin β1 / 骨転移 / 炎症

Outline of Final Research Achievements

Biological characters of cancer cells are altered responding to host responses including immune responses, and this is the essential mechanism by which cancer cells acquire resistance against various therapies. The purpose of this study is to elucidate the mechanisms that induce adaptive immune resistance by immune responses, and I have reported the following findings.
1) CD155 expressed on cancer cells and/or myeloid cells plays important role to escape anti-tumor immune responses. 2) Augmentation of DR5 surface expression overcomes the resistance against cell-death inducing cancer therapy. 3) TSLP produced by osteoblasts in inflamed micro metastasis would play roles for bone metastasis formation.

Free Research Field

腫瘍免疫学

Academic Significance and Societal Importance of the Research Achievements

癌特異的免疫反応に応答して起きる癌細胞自体の変化こそが、癌細胞が治療抵抗性となる本質的機序であり、この克服なしには治療効果には限界がある。すなわち、発癌、増殖、転移の過程における癌細胞の形質転換が癌細胞の治療抵抗性獲得の原因であることが示されている。本研究により、癌増殖過程での新たな免疫抑制分子の発現や細胞死抵抗性の新規獲得、さらには骨転移初期の炎症惹起による骨代謝制御が起きていることが示され、これらの克服が免疫療法を含む癌治療法の奏功率の向上に繋がることが示された。