Mechanisms of CD200-mediated acquisition of therapeutic resistance in colorectal cancer liver metastases and development of novel therapies.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16429
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Nara Medical University
• Principal Investigator: Matsuo Yasuko 奈良県立医科大学, 医学部, 助教 (10812315)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 大腸癌肝転移 / CD200 / 腫瘍免疫 / 治療抵抗性

Outline of Final Research Achievements

We have focused on the CD200/CD200R pathway, which is involved in T cell inactivation, and reported that in colorectal cancer liver metastasis, tumors with high CD200 expression suppress tumor immunity and have poor prognosis. On the other hand, we found that CD200 expression can be induced by chemotherapy. Furthermore, in cases undergoing chemotherapy, tumors with high CD200 expression have a very poor prognosis, and tumors with chemotherapy-induced CD200 expression may acquire resistance to existing chemotherapy. Therefore, CD200 is suggested as a potential novel therapeutic target from the perspective of tumor immunity as well as treatment resistance to existing drugs.

Free Research Field

消化器外科学

Academic Significance and Societal Importance of the Research Achievements

進行大腸癌は経過中に50-80%に肝転移を認め，肝転移の制御が大腸癌の予後改善には必須である.化学療法の進歩により予後は向上しているが，切除したとしても治癒に至る例は30%程度であり，新規治療法が望まれる．近年免疫チェックポイント阻害剤が新たな癌治療薬として効果を示している．CD200も免疫チェックポイント分子 であるが，本研究において大腸癌肝転移におけるCD200発現が腫瘍免疫を介した新たな治療ターゲットとなり得るだけでなく，既存の薬物治療に対し治療抵抗性を示す腫瘍に対しても治療ターゲットとなり得る可能性が示唆された．この結果はこれまでに報告がなく，非常に意義のある研究と思われる.