Immune status changes and prognosis after primary tumor resection in metastatic colorectal cancer

• Project/Area Number: 18K16294
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Hokkaido University
• Principal Investigator: Ichikawa Nobuki 北海道大学, 大学病院, 特任助教 (50779890)
• Project Period (FY): 2018-04-01 – 2024-03-31
• Project Status: Completed (Fiscal Year 2023)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 大腸癌 / 切除不能転移性大腸癌 / 姑息的切除 / リンパ球単球比 / 切除不能大腸癌 / 転移性大腸癌 / 切除 / 予後 / マクロファージ / リンパ球 / 腫瘍免疫

Outline of Final Research Achievements

The study examined the changes in peripheral blood lymphocyte monocyte ratio (LMR) before and after pariative colorectal resection of unresectable metastatic colorectal cancer. Of 64 patients who underwent resection of primary tumor, 39 patients had increased LMR with an average 1.57-fold increase (increased LMR group), while the remaining 25 patients had decreased LMR with an average 0.68-fold decrease (decreased LMR group). Although there were no significant differences in background factors, the median overall survival after resection in the increased LMR and decreased LMR groups was 27.3 and 20.8 months, respectively (P = 0.02). Cox regression also showed that decreased LMR was an independent poor prognostic factor. Immunostaining of specimens from primary tumor resection showed that the ratio of CD8+ to CD163+ infiltrating cells was significantly lower in cases with increased LMR.

Academic Significance and Societal Importance of the Research Achievements

切除不能転移性大腸癌において原発巣切除を行った症例の間でも、切除によりLMRの術後増加する症例は減少する症例よりは生命予後が良い可能性がある。今回、結果としてLMRが増加した症例と、減少した症例で予後及び組織学的特徴の差異を見出したが、どのような症例でLMRが増加、あるいは減少するかを術前に予見することで、原発巣切除が生命予後改善に寄与する症例を選別できる可能性がある。より症例数の多いコホートでバリデーションするとともに、本研究から得られた、組織でのCD8+：CD163+の比率を含め、より確固たる術前後LMR変化の予測因子を見出す事が今後の課題である。

Research Products

• [Journal Article] A Increase of peripheral lymphocyte-monocyte ratio after primary site resection is associated with prolonged survival in unresectable colorectal carcinoma (2019)
  • Author(s): Ichikawa N, Homma S, Yoshida T, Mitsuhashi T, Iijima H, Ogasawara K, Kazui K, Kamiizumi Y, Kawamata F, Taketomi A.
  • Journal Title: Surg Today. Volume: - Issue: 6 Pages: 604-614
  • DOI: 10.1007/s00595-019-01927-1
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Impact of Primary Tumor Resection in Colorectal Cancer with Unresectable Metastasis. (2019)
  • Author(s): Nobuki Ichikawa, Shigenori Homma, Tadashi Yoshida, Futoshi, Kawamata, Tomoko Mitsuhashi, Hiroaki Iijima, Susumu Shibasaki, Hideki Kawamura, Kazuhiro Ogasawara, Keizo Kazui, You Kamiizumi, Akinobu Taketomi
  • Organizer: 14th Academic Surgical Congress
  • Int'l Joint Research
• [Presentation] Impact of Primary Tumor Resection in Colorectal Cancer with Unresectable Metastasis (2019)
  • Author(s): Nobuki Ichikawa
  • Organizer: 14th Acaemic Surgical Congress
  • Int'l Joint Research
• [Presentation] Increase of peripheral lymphocyte-monocyte ratio after the primary site resections related with the prolonged survival in unresectable colorectal carcinoma (2018)
  • Author(s): Nobuki Ichikawa
  • Organizer: Annual Congress of European Society of Coloproctology 2018
  • Int'l Joint Research
• [Presentation] 切除不能転移性大腸癌における原発巣切除の意義の検討 (2018)
  • Author(s): 市川伸樹
  • Organizer: 日本臨床外科学会