Metastasis Control Mechanisms Based on NK Cell Suppression Mechanisms in Colorectal Cancer Patients

• Project/Area Number: 21K16446
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kobe University
• Principal Investigator: Hasegawa Hiroshi 神戸大学, 医学部附属病院, 助教 (50529542)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2022: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: NK細胞 / 遠隔転移 / 大腸癌 / 遠隔転移制御 / MDSC

Outline of Research at the Start

NK細胞抑制のメカニズムとして、Myeloid derived suppressor cell (MDSC)増加、Circulating tumor cell(CTC)のPDL1・CD47発現が考えられる。
本研究はマウスモデルと大腸癌切除検体を用いて、腫瘍をNK細胞抑制のメカニズムに基づいて分類可能であるかを明らかにすることで、分類に応じた最適な治療法を開発し、大腸癌治療成績の向上に貢献する。

Outline of Final Research Achievements

We hypothesized that tumor-induced myeloid derived suppressor cells (MDSCs) increase as colorectal cancer progresses, and that MDSCs suppress NK cell function and increase distant metastasis.A clinical study was conducted on patients with colon cancer. The main lymph node was immunostained for CD8 (CD8-positive T cells), CD33 (MDSCs), and CD56 (NK cells), and the relationship with oncological prognosis was examined. The main target of analysis was the main lymph node, but after staining 60 cases, it was found that the number of NK cells and MDSCs per field of view was difficult to evaluate because the size of the lymph node varied greatly from specimen to specimen. In addition, no correlation was observed between NK cell counts and prognosis in the patients who could be evaluated, making it difficult to carry out the original plan.

Academic Significance and Societal Importance of the Research Achievements

大腸癌患者の治療成績改善の為に遠隔転移制御は重要な課題である。遠隔転移制御機構を解明する為にNK細胞の数や機能に着目した。大腸癌患者に対する臨床研究を行い、所属リンパ節におけるNK細胞とMDSC細胞の数が予後に関連しないかについて解析を行った。
残念ながら、本研究を行った２年間の研究期間だけではこの課題に対して回答を得ることができなかったが、研究を進めていく上での問題点や解決方法についての理解が深まった。この研究結果を基に新たな研究に対する基礎研究を進めることができた。本研究を更に発展させ、2023年6月からは大腸癌患者を対象に新たな臨床研究を計画中である。

Research Products

• [Journal Article] Obesity and narrow pelvis prolong the operative time in conventional laparoscopic rectal cancer surgery, but not in a two-team transanal total mesorectal excision approach (2023)
  • Author(s): Hasegawa H, Matsuda T, Yamashita K, Sawada R, Harada H, Urakawa N, Goto H, Kanaji S, Oshikiri T, Kakeji Y.
  • Journal Title: Asian J Endosc Surg Volume: 16 Issue: 2 Pages: 189-196
  • DOI: 10.1111/ases.13134
  • Peer Reviewed
• [Journal Article] Clinical outcomes of neoadjuvant therapy followed by selective inguinal lymph node dissection and total mesorectal excision for metastasized low rectal cancer. (2022)
  • Author(s): Hasegawa H, Matsuda T, Yamashita K, Sawada R, Harada H, Urakawa N, Goto H, Kanaji S, Oshikiri T, Kakeji Y.
  • Journal Title: Langenbecks Arch Surg Volume: 408 Issue: 1 Pages: 2-2
  • DOI: 10.1007/s00423-022-02739-7
  • Peer Reviewed