細胞病理学講座【研究プロジェクト名および概要】

I. 免疫微小環境などを標的とした新規がん治療の開発
1．諸臓器悪性腫瘍の進展における腫瘍関連マクロファージ（TAM）の役割解明
2．悪性腫瘍におけるがん免疫誘導とリンパ節マクロファージの役割解明
II. ミエロイド細胞制御によりがん免疫を賦活化する化合物の探索
1．マクロファージの分化・活性化を制御する化合物の探索・合成と抗腫瘍効果の検討
III. 非腫瘍性疾患におけるマクロファージの分化・活性化に関する研究
1． マクロファージ活性化と感染症、肥満、動脈硬化、脂肪肝との関与
IV. 生検・外科切除標本、病理解剖症例を用いた外科病理学的症例解析
V.

工学部・薬学部との共同研究（医薬工連携）【教職員および大学院学生】
細胞病理学講座

大学院（博士課程）

教授

菰原義弘

D4 御任 玲美（呼吸器内科学）

講師

藤原章雄

D4 松原 恵理（呼吸器外科学）

学術研究員

潘程

D3 三浦 裕司（虎の門病院）

学術研究員

佐藤 敏美

D3 穴見 俊樹（泌尿器科学）

学術研究員

矢野

D2 李 連博浩夢（小児外科・移植外科学）

D2 石塚 志穂（呼吸器内科学）
D2 松崎 啓亮 (脳神経外科)
技術補佐員

徳永 美知代D2 江嵜 彩乃

事務補佐員

佐土原 仁美D2 平尾 洸樹（小児外科・移植外科学）

事務補佐員

村山 道子

D1 山田 倫(病理診断科)

M2 秋月 芙水花

【連絡先】 電話: 096-373-5095
Fax: 096-373-5096【ホームページ】http://srv02.medic.kumamoto-u.ac.jp/dept/patho2/patho2.html

令和元年度（2021 年度）【論文・総説】
1. Yoshii D, Nakagawa T, Komohara Y, Kawaguchi H, Yamada S, Tanimoto A. Phenotypic Changes in Macrophage Activation in a Model ofNonalcoholic Fatty Liver Disease using Microminipigs. J Atheroscler Thromb 28: 444-451, 2021.
2. Saku T, Takashio S, Tsuruta Y, Otsuka Y, Takae M, Kiyama T, Yamamoto E, Kaikita K, Hotta T, Matsumoto S, Kang D, Tsujita K, Komohara Y.
Comparison of electron microscopic findings and clinical presentation in three patients with mitochondrial cardiomyopathy caused by themitochondrial DNA mutation m.3243A > G. Med Mol Morphol 54: 181-186, 2021.
3. Kanemitsu K, Iwatsuki M, Yamashita K, Komohara Y, Morinaga T, Iwagami S, Eto K, Nagai Y, Kurashige J, Baba Y, Yoshida N, Baba H. Two
Asian families with gastric adenocarcinoma and proximal polyposis of the stomach successfully treated via laparoscopic total gastrectomy. Clin JGastroenterol 14: 92-97, 2021.
4. Liu Y, Baba Y, Ishimoto T, Tsutsuki H, Zhang T, Nomoto D, Okadome K, Yamamura K, Harada K, Eto K, Hiyoshi Y, Iwatsuki M, Nagai Y,Iwagami S, Miyamoto Y, Yoshida N, Komohara Y, Ohmuraya M, Wang X, Ajani JA, Sawa T, Baba H. Fusobacterium nucleatum confers
chemoresistance by modulating autophagy in oesophageal squamous cell carcinoma. Br J Cancer 124: 963-974, 2021.
5. Kusunoki M, Fujiwara Y, Komohara Y, Imamura Y, Honda R, Ohba T, Katabuchi H. Hemoglobin-induced continuous activation of macrophagesin endometriotic cysts: a potential mechanism of endometriosis development and carcinogenesis. Med Mol Morphol 54: 122-132, 2021.
6. Sakamoto R, Kajihara I, Mijiddorj T, Otsuka-Maeda S, Sawamura S, Nishimura Y, Kanemaru H, Kanazawa-Yamada S, Nakamura K, Honda N,Makino K, Aoi J, Igata T, Makino T, Masuguchi S, Fukushima S, Morinaga J, Komohara Y, Ihn H. Existence of Staphylococcus aureus correlateswith the progression of extramammary Paget's disease: potential involvement of interleukin-17 and M2-like macrophage polarization. Eur J
Dermatol 31: 48-54, 2021.
7. Morimoto Y, Ono S, Yoshida S, Mishima H, Kinoshita A, Tanaka T, Komohara Y, Kurotaki N, Kishino T, Okazaki Y, Ozawa H, Yoshiura KI,Imamura A. A unique missense variant in the E1A-binding protein P400 gene is implicated in schizophrenia by whole-exome sequencing and mutant
mouse models. Transl Psychiatry 11: 132, 2021.
8. Maeshiro M, Shinriki S, Liu R, Nakachi Y, Komohara Y, Fujiwara Y, Ohtsubo K, Yoshida R, Iwamoto K, Nakayama H, Matsui H. Colonization ofdistant organs by tumor cells generating circulating homotypic clusters adaptive to fluid shear stress. Sci Rep 11: 6150, 2021.
9. Kumamoto K, Tasaki T, Ohnishi K, Shibata M, Shimajiri S, Harada M, Komohara Y, Nakayama T. CD169 Expression on Lymph NodeMacrophages Predicts in Patients With Gastric Cancer. Front Oncol 11:636751, 2021.
10. Fujiwara Y, Maeda R, Takeshita H, Komohara Y. Alginates as food ingredients absorb extra salt in sodium chloride-treated mice. Heliyon 7:e06551, 2021.
11. Komohara Y, Miyamura T, Miyashita A, Shigeta H, Nakagawa T, Fukushima S. An Autopsy Case of Metastatic Melanoma Originating from theNasal Cavity That Was Treated With Nivolumab and Ipilimumab. Cancer Diagnosis and Prognosis 1: 7-12, 2021.
12. Tsukamoto H, Komohara Y, Oshiumi H. The role of macrophages in anti-tumor immune responses: pathological significance and potential astherapeutic targets. Hum Cell 34: 1031-1039, 2021.
13. Yamamura K, Beppu T, Oda E, Sato N, Yuki H, Motohara T, Miyamoto H, Miyamura S, Onishi K, Komohara Y, Akahoshi S. Hepatic
Inflammatory Pseudotumor Mimicking Malignant Tumor With Rare Onset of Intra-abdominal Hemorrhage. Anticancer Res 41: 2727-2732, 2021.
14. Sato M, Kadomatsu T, Miyata K, Warren JS, Tian Z, Zhu S, Horiguchi H, Makaju A, Bakhtina A, Morinaga J, Sugizaki T, Hirashima K,Yoshinobu K, Imasaka M, Araki M, Komohara Y, Wakayama T, Nakagawa S, Franklin S, Node K, Araki K, Oike Y. The lncRNA Caren antagonizes
heart failure by inactivating DNA damage response and activating mitochondrial biogenesis. Nat Commun 12: 2529, 2021.
15. Miura Y, Anami T, Yatsuda J, Motoshima T, Oka S, Suyama K, Inoshita N, Kinowaki K, Urakami S, Kamba T, Komohara Y. HLA-DR andCD74 Expression and the Immune Microenvironment in Renal Cell Carcinoma. Anticancer Res, 41: 2841-2848, 2021.
16. Nohara T, Fujiwara Y, El-Aasr M, Ikeda T, Ono M, Nakano D, Kinjo J. Thiolane-type sulfides from garlic, onion, and Welsh onion. J Nat Med
75: 741-751, 2021.
17. Anami T, Komohara Y, Miura Y, Yamanaka K, Kurahashi R, Segawa T, Motoshima T, Murakami Y, Yatsuda J, Yamaguchi T, Sugiyama Y,Jinnouchi Y, Kamba T. High T-cell infiltration in tumor tissue and younger age predict the response to pembrolizumab in recurrent urothelial cancer.
Med Mol Morpho 54: 316-323, 2021.
18. Matsusaka K, Fujiwara Y, Pan C, Esumi S, Saito Y, Bi J, Nakamura Y, Mukunoki A, Takeo T, Nakagata N, Yoshii D, Fukuda R, Nagasaki T,Tanaka R, Komori H, Maeda H, Watanabe H, Tamada K, Komohara Y, Maruyama T. α1-acid glycoprotein enhances the immunosuppressive andprotumor functions of tumor-associated macrophages. Cancer Res 81:4545-4559, 2021.
19. Matsubara E, Komohara Y, Shinchi Y, Mito R, Fujiwara Y, Ikeda K, Shima T, Shimoda M, Kanai Y, Sakagami T, Suzuki M. CD163-positivecancer cells are a predictor of a worse clinical course in lung adenocarcinoma. Pathol Int 71: 666-673, 2021.
20. Sato R, Imamura K, Semba T, Tomita Y, Saeki S, Ikeda K, Komohara Y, Suzuki M, Sakagami T, Saya H, Arima Y. TGF-β signaling activated bycancer-associated fibroblasts determines the histological signature of lung adenocarcinoma. Cancer Res 81: 4751-4765, 2021.
21. Fujiwara Y, Okada S, Uryu K, Maru I, Komohara Y. The extract of Ilex kudingcha inhibits atherosclerosis in apoE-deficient mice by suppressing
cholesterol accumulation in macrophages. Biosci Biotechnol Biochem 85: 2177-2184, 2021.
22. Hara Y, Yamamura K, Matsumura K, Oda E, Akahoshi S, Yuki H, Tomiguchi J, Motohara T, Miyamoto H, Komohara Y, Beppu T. Laparoscopic
Surgery for a Patient With Multiple Liver Metastases of Unknown Origin Concomitant With Gallbladder Tumor. In Vivo 35: 2963-2968, 2021.
23. Sakamoto Y, Mima K, Ishimoto T, Ogata Y, Imai K, Miyamoto Y, Akiyama T, Daitoku N, Hiyoshi Y, Iwatsuki M, Baba Y, Iwagami S,Yamashita YI, Yoshida N, Komohara Y, Ogino S, Baba H. The relationship of Fusobacterium nucleatum with antitumour immunity in colorectal
cancer liver metastasis. Cancer Sci 112: 4470-4477, 2021.
24. Yonemitsu K, Miyasato Y, Shiota T, Shinchi Y, Fujiwara Y, Hosaka S, Yamamoto Y, Komohara Y. Soluble Factors Involved in Cancer CellMacrophage Interaction Promote Breast Cancer Growth. Anticancer Res 41: 4249-4258, 2021.
25. Komohara Y, Anami T, Asano K, Fujiwara Y, Yatsuda J, Kamba T. Anti-Cancer Immune Reaction and Lymph Node Macrophage; A Review
from Human and Animal Studies. Immuno 1: 223-230, 2021.
26. Kosaka A, Ishibashi K, Nagato T, Kitamura H, Fujiwara Y, Yasuda S, Nagata M, Harabuchi S, Hayashi R, Yajima Y, Ohara K, Kumai T, Aoki N,Komohara Y, Oikawa K, Harabuchi Y, Kitada M, Kobayashi H, Ohkuri T. CD47 blockade enhances the efficacy of intratumoral STING-targetingtherapy by activating phagocytes. J Exp Med 218: e20200792, 2021.
27. Oda E, Yamamura K, Hara Y, Matsumura K, Akahoshi S, Yuki H, Motohara T, Miyamoto H, Kinoshita K, Matsumura F, Ohnishi K, Komohara
Y, Beppu T. Intrahepatic Cholangiocarcinoma Coexisting With Multiple Bile Duct Adenoma Treated as Liver Metastasis from a Pancreatic
Neuroendocrine Tumor. Anticancer Res 41: 5249-5254, 2021.
28. Iwahashi N, Ikezaki M, Fujimoto M, Komohara Y, Fujiwara Y, Yamamoto M, Mizoguchi M, Matsubara K, Watanabe Y, Matsuzaki I, Murata SI,Ihara Y, Ino K, Nishitsuji K. Lipid Droplet Accumulation Independently Predicts Poor Clinical Prognosis in High-Grade Serous Ovarian Carcinoma.
Cancers 13: 5251, 2021.
29. Carreras J, Kikuti YY, Miyaoka M, Roncador G, Garcia JF, Hiraiwa S, Tomita S, Ikoma H, Kondo Y, Ito A, Komohara Y, Nakamura N,Hamoudi R. Integrative Statistics, Machine Learning and Artificial Intelligence Neural Network Analysis Correlated CSF1R with the Prognosis ofDiffuse Large B-Cell Lymphoma. Hemato 2: 182-206, 2021.
30. Akahoshi S, Yamamura K, Komohara Y, Yoshii D, Oda E, Sato N, Yuki H, Yukimura K, Beppu T. A Case Report of Metachronous Multiple
Adenosquamous Carcinoma of the Colon Over-expressing PD-L1 and a Literature Review. Anticancer Res 41: 5847-5854, 2021.
31. Honda M, Kadohisa M, Yoshii D, Komohara Y, Hibi T. Directly recruited GATA6 + peritoneal cavity macrophages contribute to the repair ofintestinal serosal injury. Nat Commun 12: 7294, 2021.