Exploration of target molecule for immunotherapy focusing on natural immuno-system of circulating tumor cell

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K24009
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0905:Surgery of the organs maintaining homeostasis and related fields
• Research Institution: Hyogo Medical University (2020-2022); Kyoto University (2019)
• Principal Investigator: Okuno Masayuki 兵庫医科大学, 医学部, 助教 (10844011)
• Project Period (FY): 2019-08-30 – 2023-03-31
• Keywords: 循環腫瘍細胞 / 腫瘍免疫

Outline of Final Research Achievements

The current study tried to collect circulating tumor cell (CTC) in patients with metastatic colorectal cancer before and after surgery, and to analyze the differences in number of CTC and gene expression between the time before and after surgery. CTC collection from pre-operative blood sample in patients with colorectal liver metastases (CRLM) was successfully performed. However, CTC was not able to collect from post-operative blood sample.Therefore, CTC from preoperative blood samples in patients with CRLM were collected and analyzed with RNA sequencing. No significant association between gene expression of CTC and tumor characteristics, prognosis, and preoperative chemotherapy was observed.
In addition, the association between CTC induced CRLM and liver sinusoidal injury was investigated by using rat model. The result was that sinusoidal injury promoted CRLM development in CTC rat model. This might be due to the higher incidence of cancer cell implantation into the liver.

Free Research Field

腫瘍外科学

Academic Significance and Societal Importance of the Research Achievements

循環腫瘍細胞（CTC）の治療前後の自然排除機構を検討することで、CTCの免疫機構への耐性に関わる新たな分子を発見できるのではないかと考え、研究を行ったが、想定通りの結果は得られなかった。ごく少量のCTCを回収してRNA sequenceなどの解析を行うことが技術的課題であり、今後この問題をクリアすることで予定通りのCTCの免疫機構への耐性に関わる新たな分子の検討を行う必要がる。
また、別実験で肝類洞内皮細胞障害の存在下ではCTCによる肝転移形成が促進されることを確認した。化学療法等による類洞内皮障害の予防が肝転移抑制に有効であることが示唆され、今後のメカニズムの解明が必要であると考えられた。