Development of a novel immune monitoring focusing on macrophages in patients with malignancy

• Project/Area Number: 18K06991
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Kumamoto University
• Principal Investigator: Ohnishi Koji 熊本大学, 大学院生命科学研究部(医), 特任准教授 (40613378)
• Co-Investigator(Kenkyū-buntansha): 菰原 義弘 熊本大学, 大学院生命科学研究部(医), 教授 (40449921)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); 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: がん免疫 / リンパ節 / マクロファージ / CD169 / がん免疫モニタリング / 免疫モニタリング / バイオマーカー / CCL8 / CXCL10 / 免疫診断

Outline of Final Research Achievements

This study aims to develop a new immune monitoring method for predicting the effects of cancer immunotherapy. We have shown that even in patients with pancreatic cancer, gastric cancer, and tongue cancer, the higher the number of CD169-positive lymph node macrophages, the higher the postoperative survival rate. Since we have shown similar results in colorectal cancer, malignant melanoma, endometrial cancer, etc. in previous studies, CD169-positive lymph node macrophages are useful as prognostic markers in cancer patients of various cancer types. Conceivable. As a result of comprehensive analysis of humoral factors specifically produced by CD169-positive macrophages, multiple molecules such as CCL8 and CXCL10 were identified.

Academic Significance and Societal Importance of the Research Achievements

がん免疫療法は従来の手術治療や放射線・化学療法を凌駕する可能性がある新しい治療戦略であるが、劇的な治療効果を示す症例がある一方で、殆ど効果を示さない症例までその治療効果に大きな個人差が生じやすい点が問題である。そのため、治療前にがん免疫療法の効果予測が可能な免疫モニタリング法の開発が重要である。本研究では、新しい免疫モニタリング法の1つとして、リンパ節のCD169陽性マクロファージに着眼した方法を提示したことは画期的であり、今後の研究の進展により、簡便で広く応用可能ながん免疫モニタリング法の開発につなげることが可能である。

Research Products

• [Journal Article] Targeting FROUNT with disulfiram suppresses macrophage accumulation and its tumor-promoting properties (2020)
  • Author(s): Yuya Terashima, Etsuko Toda, Kouji Matsushima et al.
  • Journal Title: Nature Communications Volume: 11 Issue: 1 Pages: 1-16
  • DOI: 10.1038/s41467-020-14338-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinical impact of TROP2 in non-small lung cancers and its correlation with abnormal p53 nuclear accumulation. (2020)
  • Author(s): Mito R, Matsubara E, Komohara Y, Shinchi Y, Sato K, Yoshii D, Ohnishi K, Fujiwara Y, Tomita Y, Ikeda K, Sakagami T, Suzuki M.
  • Journal Title: Pathol Int Volume: in press Issue: 5 Pages: 287-294
  • DOI: 10.1111/pin.12911
  • Peer Reviewed
• [Journal Article] PD-L1 expression in regional lymph nodes and predictable roles in anti-cancer immune responses (2020)
  • Author(s): Komohara Y, Harada M, Ohnishi K, Kumamoto K, Nakayama T.
  • Journal Title: Journal of Clinical and Experimental Hematopathology Volume: 60 Issue: 3 Pages: 113-116
  • DOI: 10.3960/jslrt.20015
  • NAID: 130007907545
  • ISSN: 1346-4280, 1880-9952
  • Peer Reviewed
• [Journal Article] CD163 deficiency facilitates lipopolysaccharide-induced inflammatory responses and endotoxin shock in mice (2020)
  • Author(s): Fujiwara Y, Ohnishi K, Horlad H, Saito Y, Shiraishi D, Takeya H, Yoshii D, Kaieda S, Hoshino T, Komohara Y.
  • Journal Title: Clinical Translational Immunology Volume: 25 Issue: 9
  • DOI: 10.1002/cti2.1162
  • Peer Reviewed / Open Access
• [Journal Article] Accurate expression of PD-L1/L2 in lung adenocarcinoma cells: a retrospective study by double immunohistochemistry. (2019)
  • Author(s): Shinchi Y, Komohara Y, Yonemitsu K, Sato K, Ohnishi K, Saito Y, Fujiwara, Y, Mori T, Shiraishi K, Ikeda K, Suzuki M.
  • Journal Title: Cancer sci Volume: 110 Pages: 2711-2721
  • Peer Reviewed / Open Access
• [Journal Article] Transthyretin amyloid-related cerebral angiitis after liver transplantation. (2019)
  • Author(s): Yamashita T, Ohnishi K, Ueda M, Masuda T, Inoue Y, Misumi Y, Ueda A, Obayashi K, Takeya M, Ando Y.
  • Journal Title: Amyloid Volume: 26 Pages: 11-12
  • Peer Reviewed / Open Access
• [Journal Article] Maf expression in human macrophages and lymph node sinus macrophages in patients with esophageal cancer. (2019)
  • Author(s): Takeya H, Ohnishi K, Shiota T, Saito Y, Fujiwara Y, Yagi T, Kiyozumi Y, Baba Y, Yoshida N, Asano K, Tanaka M, Baba H, Komohara Y.
  • Journal Title: J Clin Exp Hematop Volume: 59 Pages: 112-118
  • NAID: 130007720030
  • Peer Reviewed / Open Access
• [Journal Article] Elevation of pulmonary CD163+ and CD204+ macrophages is associated with the clinical course of idiopathic pulmonary fibrosis patients. (2019)
  • Author(s): Nouno T, Okamoto M, Ohnishi K, Kaieda S, Tominaga M, Zaizen Y, Ichiki M, Momosaki S, Nakamura M, Fujimoto K, Fukuoka J, Shimizu S, Komohara Y, Hoshino T.
  • Journal Title: J Thorac Dis Volume: 11 Pages: 4005-4017
  • Peer Reviewed / Open Access
• [Journal Article] High CD169 expression in lymph node macrophages predicts a favorable clinical course in patients with esophageal cancer. (2018)
  • Author(s): Takeya H, Shiota T, Yagi T, Ohnishi K, Baba Y, Miyasato Y, Kiyozumi Y, Yoshida N, Takeya M, Baba H, Komohara Y.
  • Journal Title: Pathology international Volume: 68 Issue: 12 Pages: 685-693
  • DOI: 10.1111/pin.12736
  • Peer Reviewed / Open Access
• [Presentation] 敗血症モデルにおけるマクロファージCD163の炎症抑制作用. (2020)
  • Author(s): 藤原章雄、大西紘二、潘 程、中川雄伸、菰原義弘
  • Organizer: 日本薬学会 第140回年会
• [Presentation] CD169陽性リンパ節マクロファージは口腔扁平上皮癌患者のがん免疫活性化と予後を反映するマーカーになる. (2020)
  • Author(s): 大西紘二、川口翔、吉田遼司、中山秀樹、菰原義弘
  • Organizer: 第109回 日本病理学会総会
• [Presentation] 乳癌免疫微小環境におけるマクロファージの役割. (2020)
  • Author(s): 菰原義弘、米満侯宏、宮里祐子、藤原章雄、大西紘二.
  • Organizer: 第109回 日本病理学会総会
• [Presentation] 肺腺癌におけるがん細胞、マクロファージそれぞれのPD-L1/PD-L2発現の意義. (2020)
  • Author(s): 菰原義弘、西東洋一、藤原章雄、大西紘二.
  • Organizer: 第109回 日本病理学会総会
• [Presentation] Orosomucoid is indirectly involved in tumor development via macrophages. (2019)
  • Author(s): Yukio Fujiwara, Koji Ohnishi, Yoshihiro Komohara, Cheng Pan.
  • Organizer: 11th AACR-JCA Joint Conference
  • Int'l Joint Research
• [Presentation] 業務改善を目指した新しい病理診断システムの開発 (2019)
  • Author(s): 大西紘二
  • Organizer: IoMT (Internet of Medical Things) FORUM in Kyushu
• [Presentation] 環状硫黄化合物による腫瘍関連マクロファージをターゲットとしたがん治療への応用. (2019)
  • Author(s): 藤原章雄、大西紘二、菰原義弘
  • Organizer: 日本薬学会
• [Presentation] 新規バイオマーカーの探索 CD169陽性リンパ節マクロファージは膀胱癌患者の腫瘍免疫能と予後を予測する. (2019)
  • Author(s): 大西紘二、浅野桐子、菰原義弘
  • Organizer: 第108回 日本病理学会総会
• [Presentation] 新規バイオマーカーの探索 CD169陽性リンパ節マクロファージは膀胱癌患者の腫瘍免疫能と予後を予測する. (2019)
  • Author(s): 大西紘二、浅野桐子、菰原義弘.
  • Organizer: 第108回 日本病理学会総会