Morphological and spatial pattern analysis of tumor associated macrophages in hepatocelluar carcinoma by imaging AI

• Project/Area Number: 22K08008
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: University of Fukui
• Principal Investigator: 平松 活志 福井大学, 学術研究院医学系部門, 客員准教授 (30646849)
• Project Period (FY): 2022-04-01 – 2025-03-31
• Project Status: Granted (Fiscal Year 2022)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2024: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 免疫担当細胞 / 人工知能 / 腫瘍関連マクロファージ

Outline of Research at the Start

本研究では、肝がん組織で蛍光多重染色したTAMを人工知能による画像解析技術（イメージングAI）を駆使して解析する。すなわち、TAMの形態的特徴とその分布、他の細胞との空間的相互作用、さらに細胞内代謝遺伝子などの蛍光多重 in situ hybridizationのデータを統合した空間的遺伝子発現パターンの解析を行う。これより、肝がんにおけるTAMの形態的多様性（morphology）や機能的可塑性(plasticity)に関連するユニークな治療ターゲットの同定に繋がる可能性がある。

Outline of Annual Research Achievements

C型肝炎治療後の肝癌患者７１例を対象とし、手術にて得られた肝癌組織を蛍光多重染色した。腫瘍内や周囲組織およびその境界に浸潤する免疫担当細胞を画像解析技術（イメージングAI）を駆使して解析する方法を確立した。 空間プロファイリング解析においては、腫瘍内被膜下（SC）のCD4(+)Tリンパ球と周囲非腫瘍部（A）の制御性Tリンパ球（Treg）との細胞間相互作用（クロストーク）が長期予後に影響する可能性が示唆された。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

研究計画書における、本年度の予定としては、蛍光多重免疫染色とイメージングAIを用いた、免疫担当細胞の形態学的フェノタイプ解析となっており、おおむね順調に進展していると判断する。

Strategy for Future Research Activity

当初の研究計画どおり、組織フェノタイプ機械学習とNGS遺伝子発現解析によって、肝癌微小環境における免疫担当細胞の役割を検討する。

Research Products

• [Journal Article] Hepatocellular carcinoma progression promoted by 5-lipoxygenase activity in CD163(+) tumor-associated macrophages. (2023)
  • Author(s): Nosaka T, Murata Y, Takahashi K, Naito T, Ofuji K, Matsuda H, Ohtani M, Hiramatsu K, Imamura Y, Goi T, Nakamoto Y
  • Journal Title: Biomed Pharmacother. Volume: 162 Pages: 114592-114592
  • DOI: 10.1016/j.biopha.2023.114592
  • Peer Reviewed / Open Access
• [Journal Article] Histology and cytokine levels in hepatic injury accompanying a case of non-severe COVID-19. (2023)
  • Author(s): Matsuda H, Nosaka T, Hiramatsu K, Takahashi K, Naito T, Ofuji K, Ohtani M, Imamura Y, Iwasaki H, Nakamoto Y.
  • Journal Title: Clin J Gastroenterol. Volume: 16(2) Issue: 2 Pages: 270-278
  • DOI: 10.1007/s12328-023-01755-4
  • Peer Reviewed / Open Access
• [Journal Article] Elderly onset congenital hepatic fibrosis with portal hypertension diagnosed after recurrent cholangitis: a case report (2022)
  • Author(s): Takahashi Kazuto、Ofuji Kazuya、Nosaka Takuto、Naito Tatsushi、Matsuda Hidetaka、Ohtani Masahiro、Hiramatsu Katsushi、Harada Kenichi、Naiki Hironobu、Nakamoto Yasunari
  • Journal Title: Clinical Journal of Gastroenterology Volume: 15 Issue: 3 Pages: 611-616
  • DOI: 10.1007/s12328-022-01620-w
  • Peer Reviewed / Open Access
• [Journal Article] Successful early diagnosis of monomorphic epitheliotropic intestinal T-cell lymphoma manifesting as chronic diarrhea and hypokalemia using video capsule endoscopy and double-balloon enteroscopy. (2022)
  • Author(s): Naito T, Nosaka T, Takahashi K, Ofuji K, Matsuda H, Ohtani M, Hiramatsu K, Imamura Y, Yamauchi T, Nakamoto Y.
  • Journal Title: Clin J Gastroenterol. Volume: 15(5) Issue: 5 Pages: 913-919
  • DOI: 10.1007/s12328-022-01676-8
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A rare case of eosinophilic gastritis induced by nivolumab therapy for metastatic melanoma. (2022)
  • Author(s): Tsuji A, Hiramatsu K, Namikawa S, Yamamoto A, Midori Y, Murata Y, Tanaka T, Nosaka T, Naito T, Takahashi K, Ofuji K, Matsuda H, Ohtani M, Imamura Y, Iino S, Hasegawa M, Nakamoto Y.
  • Journal Title: Clin J Gastroenterol. Volume: 5(5) Issue: 5 Pages: 876-880
  • DOI: 10.1007/s12328-022-01680-y
  • Peer Reviewed / Open Access
• [Journal Article] Cholesterol crystal embolism in multiple organs after transarterial chemoembolization for hepatocellular carcinoma: An autopsy case report. (2022)
  • Author(s): Yamashita J, Nosaka T, Takahashi K, Naito T, Ofuji K, Matsuda H, Ohtani M, Hiramatsu K, Kobayashi M, Nakamoto Y.
  • Journal Title: Medicine (Baltimore) Volume: 101(39) Issue: 39 Pages: e30769-e30769
  • DOI: 10.1097/md.0000000000030769
  • Peer Reviewed / Open Access
• [Journal Article] Regulatory function of interferon‐inducible 44‐like for hepatitis B virus covalently closed circular DNA in primary human hepatocytes (2021)
  • Author(s): Nosaka Takuto、Naito Tatsushi、Murata Yosuke、Matsuda Hidetaka、Ohtani Masahiro、Hiramatsu Katsushi、Nishizawa Tsutomu、Okamoto Hiroaki、Nakamoto Yasunari
  • Journal Title: Hepatology Research Volume: 52 Issue: 2 Pages: 141-152
  • DOI: 10.1111/hepr.13722
  • Peer Reviewed / Open Access
• [Presentation] Clinical Usefulness of Skeletal Muscle Quantity as Prognostic Factor in Elderly Patients with Advanced Pancreatic Cancer Receiving Nab-Paclitaxel Plus Gemcitabine Chemotherapy (2022)
  • Author(s): Akazawa Y, Ohtani M, Nosaka T, Takahashi K, Naito T, Ofuji K, Matsuda H, Hiramatsu K, Nakamoto Y
  • Organizer: DDW 2022
  • Int'l Joint Research
• [Presentation] Risk Factors for Pancreatic Malignancies in Patients with Low-Risk Branch Duct Intraductal Papillary Mucinous Neoplasms after 5 Years of Long-Term Follow-Up (2022)
  • Author(s): Ohtani M, Ofuji K, Akazawa Y, Nosaka T, Takahashi K, Naito T, Matsuda H, Hiramatsu K, Nakamoto Y
  • Organizer: DDW 2022
  • Int'l Joint Research
• [Presentation] Analysis of Mucosa-Associated Dysbiosis Related to Bile Acid Metabolism in Post-SVR Hepatitis C Patients Complicated with Esophageal Varices (2022)
  • Author(s): Midori Y, Hiramatsu K, Nosaka T, Akazawa Y, Takahashi K, Naito T, Matsuda H, Ohtani M, Nakamoto Y
  • Organizer: AASLD 2022
  • Int'l Joint Research