The significance of macrophages in several diseases

• Project/Area Number: 16H05162
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human pathology
• Research Institution: Kumamoto University
• Principal Investigator: Komohara Yoshihiro 熊本大学, 大学院生命科学研究部(医), 准教授 (40449921)
• Co-Investigator(Kenkyū-buntansha): 哈 斯塔 (Horlad Hasita) 熊本大学, 大学院生命科学研究部(医), 研究員 (00644840) ; 浅野 謙一 東京薬科大学, 生命科学部, 准教授 (10513400) ; 大西 紘二 熊本大学, 大学院生命科学研究部(医), 特任准教授 (40613378) ; 藤原 章雄 熊本大学, 大学院生命科学研究部(医), 講師 (70452886)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000); Fiscal Year 2019: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2018: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2017: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2016: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
• Keywords: がん / マクロファージ / がん免疫 / CD163 / CD169

Outline of Final Research Achievements

We demonstrated the significance of macrophages in solid tumors, and association between anti-cancer immune responses and macrophage activation.

Academic Significance and Societal Importance of the Research Achievements

様々な悪性腫瘍におけるマクロファージの役割と治療抵抗性への関与、あるいはがん免疫との関連性について解析し、それをもとに治療法の開発やあらたな解析方法の開発を行った。

Research Products

• [Journal Article] Accurate expression of PD‐L1/L2 in lung adenocarcinoma cells: A retrospective study by double immunohistochemistry (2019)
  • Author(s): Shinchi Yusuke、Komohara Yoshihiro、Yonemitsu Kimihiro、Sato Kensaku、Ohnishi Koji、Saito Yoichi、Fujiwara Yukio、Mori Takeshi、Shiraishi Kenji、Ikeda Koei、Suzuki Makoto
  • Journal Title: Cancer Science Volume: 110 Issue: 9 Pages: 2711-2721
  • DOI: 10.1111/cas.14128
  • Peer Reviewed / Open Access
• [Journal Article] Expression of IL-34 correlates with macrophage infiltration and prognosis of diffuse large B-cell lymphoma. (2019)
  • Author(s): Noyori O, Komohara Y (**), Nasser H, Hiyoshi M, Ma C, Pan C, Carreras J, Nakamura N, Sato A, Ando K, Okuno Y, Nosaka K, Matsuoka M, Suzu S
  • Journal Title: Clin Transl Immunology Volume: 8
  • Peer Reviewed
• [Journal Article] Positive correlation between the density of macrophages and T-cells in undifferentiated sarcoma (2018)
  • Author(s): Komohara Yoshihiro、Takeya Hiroto、Wakigami Nanako、Kusada Natsuki、Bekki Hirofumi、Ishihara Shin、Takeya Motohiro、Nakashima Yasuharu、Oda Yoshinao
  • Journal Title: Medical Molecular Morphology Volume: 52 Issue: 1 Pages: 44-51
  • DOI: 10.1007/s00795-018-0201-3
  • Peer Reviewed
• [Journal Article] Down-regulation of 15-PGDH by interleukin-1 beta from activated macrophages leads to poor prognosis in pancreatic cancer. (2018)
  • Author(s): Arima K, Komohara Y, Bu L, Tsukamoto M, Itoyama R, Miyake K, Uchihara T, Ogata T, Nakagawa Y, Okabe S, Imai K, Hashimoto D, Chikamoto A, Yamashita Y, Baba H, Ishimoto T.
  • Journal Title: Cancer Sci. 109;462-470, 2018. Volume: 109 Pages: 462-462
  • Peer Reviewed / Open Access
• [Journal Article] CD163-positive cancer cells are potentially associated with high malignant potential in clear cell renal cell carcinoma (2018)
  • Author(s): Ma C, Horlad H, Ohnishi K, Nakagawa T, Yamada S, Kitada S, Motoshima T, Kamba T, Nakayama T, Takeya M, Komohara Y (**).
  • Journal Title: Med Mol Morphol. 51:13-20, 2018. Volume: 51 Pages: 13-13
  • Peer Reviewed
• [Journal Article] Phenotypical change of tumor-associated macrophages in metastatic lesions of clear cell renal cell carcinoma. (2018)
  • Author(s): Motoshima T, Miura Y, Wakigami N, Kusada N, Takano T, Inoshita N, Okaneya T, Sugiyama Y, Kamba T, Takeya M, Komohara Y (**).
  • Journal Title: Med Mol Morphol. 51:57-63. 2018. Volume: 51 Pages: 57-57
  • Peer Reviewed
• [Journal Article] Natural compounds that regulate lymph node sinus macrophages: Inducing an anti-tumor effect by regulating macrophage activation. (2018)
  • Author(s): Fujiwara Y, Saito Y, Shiota T, Cheng P, Ikeda T, Ohnishi K, Takeya M, Komohara Y (**).
  • Journal Title: J Clin Exp Hematop. 58:17-23, 2018. Volume: 58 Pages: 17-17
  • NAID: 130006512988
  • Peer Reviewed / Open Access
• [Journal Article] Oligodendrocyte progenitor cells and macrophages/microglia produce glioma stem cell niches at the tumor border. (2018)
  • Author(s): Hide T, Komohara Y, Miyasato Y, Nakamura H, Makino K, Takeya M, Kuratsu J, Mukasa A, Yano S.
  • Journal Title: EBioMedicine 30:94-104, 2018. Volume: 30 Pages: 94-94
  • Peer Reviewed
• [Journal Article] CD163 is required for protumoral activation of macrophages in human and murine sarcoma. (2018)
  • Author(s): Shiraishi D, Fujiwara Y, Horlad H, Saito Y, Iriki T, Tsuboki J, Pan C, Nakagata N, Mizuta H, Bekki H, Nakashima Y, Oda Y, Takeya M, Komohara Y (**).
  • Journal Title: Cancer Res. 78;3255-3266, 2018 Volume: 78 Pages: 3255-3255
  • Peer Reviewed
• [Journal Article] CD169-positive sinus macrophages in the lymph nodes determine bladder cancer prognosis. (2018)
  • Author(s): Asano T, Ohnishi K, Shiota T, Motoshima T, Sugiyama Y, Yatsuda J, Kamba T, Ishizaka K, Komohara Y (**).
  • Journal Title: Cancer Sci 109;1723-1730, 2018 Volume: 109 Pages: 1723-1723
  • Peer Reviewed / Open Access
• [Journal Article] The expression of PD-1 ligands and IDO1 by macrophages/microglia in primary central nervous system lymphoma. (2018)
  • Author(s): Miyasato Y, Takashima Y, Takeya H, Yano H, Hayano A, Nakagawa T, Makino K, Takeya M, Yamanaka R, Komohara Y (**).
  • Journal Title: J Clin Exp Hematop. 58:95-101, 2018. Volume: 58 Pages: 95-95
  • NAID: 130007403913
  • Peer Reviewed / Open Access
• [Journal Article] Potential anti-lymphoma effect of M-CSFR inhibitor in adult T-cell leukemia/lymphoma. (2018)
  • Author(s): Komohara Y (**), Noyori O, Saito Y, Takeya H, Baghdadi M, Kitagawa M, Hama N, Ishikawa K, Okuno Y, Nosaka K, Seino K, Matsuoka M, Suzu S
  • Journal Title: J Clin Exp Hematop. 58: 152-160, 2018. Volume: 58 Pages: 152-152
  • NAID: 130007529824
  • 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: Pathol Int 68: 685-693, 2018. Volume: 68 Pages: 685-685
  • Peer Reviewed
• [Journal Article] Possible functions of CD169-positive sinus macrophages in lymph nodes in anti-tumor immune responses (2017)
  • Author(s): Komohara Y, Ohnishi K, Takeya M
  • Journal Title: Cancer Sci Volume: 108; Pages: 290-295
  • Peer Reviewed / Open Access
• [Journal Article] The cell-cell interaction between tumor-associated macrophages and small cell lung cancer cells is involved in tumor progression via STAT3 activation. (2017)
  • Author(s): Iriki T, Ohnishi K, Fujiwara Y, Horlad H, Saito Y, Ikeda K, Mori T, Suzuki M, Ichiyasu H, Kohrogi H, Takeya M, Komohara Y
  • Journal Title: Lung Cancer Volume: 106,
  • Peer Reviewed
• [Journal Article] Cell adhesion molecule-1 (CADM1) expressed on adult T-cell leukemia/lymphoma cells is not involved in the interaction with macrophages (2017)
  • Author(s): Komohara Y, Ma, C, Yano H, Pan C, Horlad H, Saito Y, Ohnishi K, Fujiwara Y, Okuno Y, Nosaka K, Shinosaki S, Morishita K, Matsuoka M, Wakayama T, Takeya M.
  • Journal Title: J Clin Exp Hematop. Volume: 57:
  • NAID: 130005709559
  • Peer Reviewed / Open Access
• [Journal Article] Optimum immunohistochemical procedures for analysis of macrophages in human and mouse formalin fixed paraffin-embedded tissue samples. (2017)
  • Author(s): Nakagawa T, Ohnishi K, Kosaki Y, Saito Y, Horlad H, Fujiwara Y, Takeya M, Komohara Y
  • Journal Title: J Clin Exp Hematop. Volume: 57:
  • NAID: 130005709518
  • Peer Reviewed / Open Access
• [Journal Article] The high density of CD204-positive macrophages predicts worse clinical prognosis in patients with breast cancer. (2017)
  • Author(s): Miyasato Y, Shiota T, Ohnishi K, Pan C, Yano H, Horlad H, Yamamoto Y, Yamamoto-Ibusuki M, Iwase H, Takeya M, Komohara Y
  • Journal Title: Cancer Sci. Volume: 108;
  • Peer Reviewed / Open Access
• [Journal Article] Guanylate-binding protein 5 is a marker of interferon-γ-induced classically activated macrophages (2016)
  • Author(s): Fujiwara Y, Hizukuri Y, Yamashiro K, Makita N, Ohnishi K, Takeya M, Komohara Y
  • Journal Title: Clin Transl Immunology 5:e111, 2016. Volume: 5
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] An IL-27/Stat3 axis induces expression of programmed cell death 1 ligands (PD-L1/2) on infiltrating macrophages in lymphoma (2016)
  • Author(s): Horlad H, Ma C, Yano H, Pan C, Ohnishi K, Fujiwara Y, Endo S, Kikukawa Y, Okuno Y, Matsuoka M, Takeya M, Komohara Y
  • Journal Title: ancer Sci 107:1696-1704, 2016. Volume: 107 Pages: 1696-1704
  • NAID: 120006223644
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Onionin A, a sulfur-containing compound isolated from onions, impairs tumor development and lung metastasis by inhibiting the protumoral and immunosuppressive functions of myeloid cells. (2016)
  • Author(s): Fujiwara Y, Horlad H, Shiraishi D, Tsuboki J, Kudo R, Ikeda T, Nohara T, Takeya M, Komohara Y
  • Journal Title: Mol Nutr Food Res 60:2467-2480, 2016. Volume: 60
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] . The Clinical Significance of CD169-Positive Lymph Node Macrophage in Patients with Breast Cancer. (2016)
  • Author(s): Shiota T, Miyasato Y, Ohnishi K, Yamamoto-Ibusuki M, Yamamoto Y, Iwase H, Takeya M, Komohara Y
  • Journal Title: PLoS One. 2016; 11: e0166680. Volume: 11
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] TIM-3 expression in lymphoma cells predicts chemoresistance in patients with adult T-cell leukemia/lymphoma (ATLL). (2016)
  • Author(s): Horlad H, Ohnishi K, Ma C, Fujiwara Y, Niino D, Ohshima K, Jinushi M, Matsuoka M, Takeya M, Komohara Y
  • Journal Title: Oncol Lett 12: 1519-1524, 2016 Volume: 12 Pages: 1519-1524
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 肺癌におけるマクロファージ浸潤の意義―特にがん免疫との接点について (2019)
  • Author(s): 菰原義弘
  • Organizer: 日本病理学会 第65回秋期特別総会 コンパニオンミーティング
  • Invited
• [Presentation] がんの免疫療法耐性メカニズムと新たな治療戦略 (2019)
  • Author(s): 菰原義弘
  • Organizer: 第41回熊本大学病院臨床カンファレンス
  • Invited
• [Presentation] がん免疫におけるマクロファージの役割 (2018)
  • Author(s): 菰原義弘
  • Organizer: 第46回臨床免疫学会総会 2018年11月8日～10日 軽井沢プリンスホテル （軽井沢）
  • Invited
• [Presentation] 未分化肉腫における免疫細胞とCD163の重要性 (2018)
  • Author(s): Yoshihiro Komohara, Daisuke Shiraishi, Hiroto Takeya, Yasuharu Nakashima, Yoshinao Oda, Hiroshi Mizuta, Yukio Fujiwara, The significance of CD163 in tumor immune microenvironment (TIME) in undifferentiated sarcoma
  • Organizer: 第3回日本肉腫学会 2018年12月12日～13日、東京コンペンションホール（東京）
• [Presentation] がんにおけるマクロファージの役割：細胞間相互作用の重要性. (2018)
  • Author(s): 菰原義弘.
  • Organizer: 第16回 がんとハオポキシア研究会 2018年11月9日ホテルグリーンタワー幕張（千葉）
  • Invited
• [Presentation] M2-likeマーカーであるCD163はマクロファージの腫瘍促進性活性化に関与する (2018)
  • Author(s): 菰原義弘、白石大偉輔、西東洋一、Horlad Hasita、藤原章雄
  • Organizer: 第22回日本がん免疫学会総会 2018年8月1日～3日 岡山コンペンションセンター （岡山）
• [Presentation] がん免疫におけるマクロファージ・ミエロイド系細胞の役割 (2018)
  • Author(s): 菰原義弘
  • Organizer: 第107回日本病理学会総会2018年6月21日～23日 ロイトン札幌（札幌）
  • Invited
• [Presentation] IL-34 induces cell migration, and its ectopic expression correlates with macrophage infiltration and prognosis of DLBCL. (2018)
  • Author(s): Komohara Y, Noyori O, Ma C, Pan C, Carreras J, Nakamura N, Sato A, Ando K, Okuno Y, Nosaka N, Matsuoka M, Takeya M, Suzu S.
  • Organizer: The 14th Japanese-Korean Lymphoreticular Workshop 2018 2018/1/26-27 The Prince Hakone Lake Ashinoko (Kanagawa, Japan)
  • Int'l Joint Research
• [Presentation] The significance of lymph node macrophages in the induction of anti-cancer immune response (2017)
  • Author(s): Komohara Y, Saito Y, Shiota T, Ohnishi K, Takeya M.
  • Organizer: 36th Sapporo International Cancer Symposium,
  • Int'l Joint Research
• [Presentation] 菰原義弘、馬超亜、潘程、Carreras Joaquim, 中村直哉、竹屋元裕 (2017)
  • Author(s): 菰原義弘
  • Organizer: 第57回日本リンパ網内系学会
• [Presentation] 脳原発悪性リンパ腫におけるマクロファージ/ミクログリアの役割 (2017)
  • Author(s): 菰原義弘
  • Organizer: 第58回日本神経病理学会
• [Presentation] Multiple functions of macrophages in human diseases. (2017)
  • Author(s): 菰原義弘
  • Organizer: Kumamoto Symposium on Therapeutic/Diagnosis Techniques and Medical Devices.
  • Invited
• [Presentation] B細胞性リンパ腫におけるIL-34の重要性 (2017)
  • Author(s): 菰原義弘、馬超亜、潘程、Carreras Joaquim, 中村直哉、竹屋元裕
  • Organizer: 第106回日本病理学会総会
• [Presentation] ヒトがん・肉腫の病態とがん免疫におけるマクロファージの役割 (2016)
  • Author(s): 菰原義弘
  • Organizer: 第1回日本肉腫学会総会 2016年12月1日～2日（京都平安ホテル、京都）
  • Place of Presentation: 京都
  • Year and Date: 2016-12-01
  • Invited
• [Presentation] Inhibitory effect on Lymphoma Cell Proliferation by Regulating Cholesterol Metabolism Pathway (2016)
  • Author(s): Yukio Fujiwara, Hasita Horlad, Daisuke Niino, Yutaka Okuno, Kikukawa Yoshitaka, Masao Matsuoka, Motohiro Takeya, Yoshihiro Komohara,
  • Organizer: THE 1ST MEETING OF THE YONGLIN HEALTHCARE SYMPOSIUM SERIES-“DNA PROCESSES, DRUGS AND CANCER” 2016/11/27-28 National Taiwan University, Taiwan
  • Place of Presentation: 台北
  • Year and Date: 2016-11-27
  • Int'l Joint Research
• [Presentation] Infiltrating Macrophages Express PD-L1 and PD-L2 in Lymphoma Microenvironment (2016)
  • Author(s): Yoshihiro Komohara, Hasita Horlad, Chaoya Ma, Shinya Endo, Yoshitaka Kikukawa, Yutaka Okuno, Masao Matsuoka, Motohiro Takeya
  • Organizer: THE 1ST MEETING OF THE YONGLIN HEALTHCARE SYMPOSIUM SERIES-“DNA PROCESSES, DRUGS AND CANCER” 2016/11/27-28 National Taiwan University, Taiwan
  • Place of Presentation: 台北
  • Year and Date: 2016-11-27
  • Int'l Joint Research
• [Presentation] コレステロール排出経路を標的とした新たながん治療戦略 (2016)
  • Author(s): 菰原義弘、藤原章雄、Horlad Hasita 、矢野浩夢、潘程、竹屋元裕
  • Organizer: 第48回日本臨床分子形態学会総会 2016年9月23日～24日（くまもと県民交流会館パレア、熊本）
  • Place of Presentation: 熊本
  • Year and Date: 2016-09-23
  • Invited
• [Presentation] ヒト悪性腫瘍におけるマクロファージの役割―がん免疫との接点 (2016)
  • Author(s): 菰原義弘
  • Organizer: 第44回 日本臨床免疫学会総会 2016年9月8日～10日（京王プラザホテル、東京）
  • Place of Presentation: 東京
  • Year and Date: 2016-09-08
  • Invited