Development of genetically modified iPS cell derived M1 macrophage therapy against melanoma

• Project/Area Number: 18K08301
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Kumamoto University
• Principal Investigator: FUKUSHIMA SATOSHI 熊本大学, 大学院生命科学研究部(医), 教授 (50398210)
• Co-Investigator(Kenkyū-buntansha): 尹 浩信 熊本大学, 大学院生命科学研究部(医), 教授 (20282634)
• 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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: メラノーマ / iPS細胞 / マクロファージ / がん免疫療法 / 腫瘍微小環境 / 免疫細胞療法 / サイトカイン / 免疫チェックポイント分子 / 4-1BBL / 抗原特異性 / 免疫細胞治療 / 免疫療法 / 細胞移入療法

Outline of Final Research Achievements

We reported the efficacy of an immune cell therapy with immortalized myeloid cells derived from induced pluripotent stem cells (iPS-ML). We generated OX40L-overexpressing iPS-MP (iPS-MP-OX40L) and investigated their characteristics and in vivo efficacy against mouse melanoma. We found that iPS-ML-Zsgreen-OX40L suppressed the progression of B16-BL6 melanoma, and prolonged survival of mice with ovalbumin (OVA)-expressing B16 melanoma (MO4). The number of antigen-specific CD8+ T cells
was higher in spleen cells treated with OVA peptide-pulsed iPS-MP-OX40L than in those without OX40L. The OVA peptide-pulsed iPS-MP-OX40L significantly increased the number of tumor-infiltrating T lymphocytes in MO4 tumor. Flow cytometry showed decreased regulatory T cells but increased effector
and effector memory T cells among the TILs.

Academic Significance and Societal Importance of the Research Achievements

近年、がん免疫療法の有効性が明らかとなっていが、その有効率は未だ十分ではない。どうやったら現在の免疫療法が無効な患者に対して、有効な治療法を確立することができるか、その答えのひとつとして、iPS細胞を用いた遺伝子改変免疫細胞療法を提案する。免疫を活性化する分子を発現させたiPS細胞由来マクロファージはマウスモデルで強い効果を示した。またその安全性も確認した。

Research Products

• [Journal Article] Existence of Staphylococcus aureus correlates with the progression of extramammary Paget's disease: potential involvement of interleukin-17 and M2-like macrophage polarization (2021)
  • Author(s): R. Sakamoto, I. Kajihara, T. Mijiddorj, S. Otsuka-Maeda, S. Sawamura, Y. Nishimura, H. Kanemaru, S. Kanazawa-Yamada, K. Nakamura, N. Honda, K. Makino, J. Aoi, T. Igata, T. Makino, S. Masuguchi, S. Fukushima, J. Morinaga, Y. Komohara, H. Ihn
  • Journal Title: European Journal of Dermatology Volume: 1;31(1) Issue: 1 Pages: 48-54
  • DOI: 10.1684/ejd.2021.3972
  • Peer Reviewed
• [Journal Article] Immune cell therapy against disseminated melanoma by utilizing induced pluripotent stem cell-derived myeloid cell lines producing interferon-beta or interleukin-15/interleukin-15 receptor alpha (2021)
  • Author(s): Mizuhashi S, Kubo Y, Fukushima S, Kanemaru H, Nakahara S, Miyasita A, Ishibashi T, Kuriyama H, Kimura T, Masuguchi S, Zhang R, Iwama T, Nakatsura T, Uemura Y, Senju S, Ihn H.
  • Journal Title: J Dermatol Sci. Volume: - Issue: 2 Pages: 133-136
  • DOI: 10.1016/j.jdermsci.2021.03.005
  • Peer Reviewed
• [Journal Article] Improved safety of induced pluripotent stem cell-derived antigen-presenting cell-based cancer immunotherapy (2021)
  • Author(s): Mashima H, Zhang R, Kobayashi T, Tsukamoto H, Liu T, Iwama T, Hagiya Y, Yamamoto M, Fukushima S, Okada S, Idiris A, Kaneko S, Nakatsura T, Ohdan H, Uemura Y.
  • Journal Title: Mol Ther Methods Clin Dev . Volume: 21 Pages: 171-179
  • DOI: 10.1016/j.omtm.2021.03.002
  • Peer Reviewed / Open Access
• [Journal Article] Five-year survival with nivolumab in previously untreated Japanese patients with advanced or recurrent malignant melanoma (2021)
  • Author(s): Uhara H, Kiyohara Y, Uehara J, Fujisawa Y, Takenouchi T, Otsuka M, Uchi H, Fukushima S, Minami H, Hatsumichi M, Yamazaki N.
  • Journal Title: J Dermatol . Volume: 48 Issue: 5 Pages: 592-599
  • DOI: 10.1111/1346-8138.15804
  • Peer Reviewed / Open Access
• [Journal Article] Immunotherapy with 4-1BBL-Expressing iPS Cell-Derived Myeloid Lines Amplifies Antigen-Specific T Cell Infiltration in Advanced Melanoma (2021)
  • Author(s): Kuriyama H, Fukushima S, Kimura T, Kanemaru H, Miyashita A, Okada E, Kubo Y, Nakahara S, Tokuzumi A, Nishimura Y, Kajihara I, Makino K, Aoi J, Masuguchi S, Tsukamoto H, Inozume T, Zhang R, Nakatsura T, Uemura Y, Senju S, Ihn H.
  • Journal Title: Int J Mol Sci . Volume: 22(4) Issue: 4 Pages: 1958-1958
  • DOI: 10.3390/ijms22041958
  • Peer Reviewed / Open Access
• [Journal Article] Nucleosome assembly protein 1-like 4, a new therapeutic target for proliferation and invasion of melanoma cells (2021)
  • Author(s): Mizuhashi S, Fukushima S, Ishibashi T, Kuriyama H, Kimura T, Kanemaru H, Kajihara I, Makino K, Miyashita A, Aoi J, Kita K, Ihn H.
  • Journal Title: J Dermatol Sci . Volume: - Issue: 1 Pages: 16-24
  • DOI: 10.1016/j.jdermsci.2021.02.001
  • Peer Reviewed
• [Journal Article] Methyl-CpG binding domain protein 3: a new diagnostic marker and potential therapeutic target of melanoma (2020)
  • Author(s): Takayuki Ishibashi, Ikko Kajihara, Satoru Mizuhashi, Haruka Kuriyama, Toshihiro Kimura, Hisashi Kanemaru, Katsunari Makino, Azusa Miyashita, Jun Aoi, Takamitsu Makino, Satoshi Fukushima, Kanako Kita, Hironobu Ihn
  • Journal Title: BioScience Trends Volume: 14 Issue: 5 Pages: 390-395
  • DOI: 10.5582/bst.2020.01048
  • NAID: 130007935965
  • ISSN: 1881-7815, 1881-7823
  • Year and Date: 2020-10-31
  • Peer Reviewed / Open Access
• [Journal Article] Non-small-cell Lung Cancer with Severe Skin Manifestations Related to Radiation Recall Dermatitis after Atezolizumab Treatment (2020)
  • Author(s): Nakashima K, Saruwatari K, Sato R, Imamura K, Kajihara I, Fukushima S, Saito T, Ishizuka S, Tamanoi D, Jodai T, Hamada S, Tomita Y, Saeki S, Ichiyasu H, Oya N, Ihn H, Sakagami T.
  • Journal Title: Internal Medicine Volume: 59 Issue: 9 Pages: 1199-1202
  • DOI: 10.2169/internalmedicine.3937-19
  • NAID: 130007839434
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2020-05-01
  • Peer Reviewed / Open Access
• [Journal Article] Concordance and Discordance Rates of V-Raf Murine Sarcoma Viral Oncogene Homolog B1 (BRAF) V600E Status in Metastatic against Primary Lesion of Melanoma: A Meta-analysis (2020)
  • Author(s): Yokomichi H, Inozume T, Wada M, Asai J, Igaki H, Namikawa K, et al.
  • Journal Title: JMA Journal Volume: 3 Issue: 3 Pages: 274-279
  • DOI: 10.31662/jmaj.2020-0016
  • NAID: 130007905834
  • Peer Reviewed / Open Access
• [Journal Article] miR-524-5p reduces the progression of the BRAF inhibitor-resistant melanoma (2020)
  • Author(s): Nguyen MT, Lin CH, Liu SM, Miyashita A, Ihn H, Lin H, Ng CH, Tsai JC, Chen MH, Tsai MS, Lin IY, Liu SC, Li LY, Fukushima S, Lu J, Ma N.
  • Journal Title: Neoplasia . Volume: 22 Issue: 12 Pages: 789-799
  • DOI: 10.1016/j.neo.2020.10.009
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Skin microbiome in acral melanoma: Corynebacterium is associated with advanced melanoma (2020)
  • Author(s): Mizuhashi S, Kajihara I, Sawamura S, Kanemaru H, Makino K, Aoi J, Makino T, Masuguchi S, Fukushima S, Ihn H.
  • Journal Title: J Dermatol . Volume: 48 Issue: 1
  • DOI: 10.1111/1346-8138.15633
  • Peer Reviewed
• [Journal Article] Matrin-3 plays an important role in cell cycle and apoptosis for survival in malignant melanoma (2020)
  • Author(s): Haruka Kuriyama, Satoshi Fukushima, Toshihiro Kimura, Etsuko Okada, Takayuki Ishibashi, Satoru Mizuhashi, Hisashi Kanemaru, Ikko Kajihara, Katsunari Makino, Azusa Miyashita, Jun Aoi, Seiji Okada, Hironobu Ihn, Kanako Kita
  • Journal Title: Journal of Dermatological Science Volume: 100(2) Issue: 2 Pages: 110-119
  • DOI: 10.1016/j.jdermsci.2020.08.013
  • Peer Reviewed
• [Journal Article] Single administration of avelumab induced a complete response in thyroid transcription factor-1 positive combined Merkel cell carcinoma (2020)
  • Author(s): Hisashi Kanemaru, Satoshi Fukushima, Yukari Mizukami, Soichiro Sawamura, Kayo Nakamura, Noritoshi Honda, Katsunari Makino, Ikko Kajihara, Jun Aoi, Takamitsu Makino, Takeshi Kawasaki, Erina Kudou, Masayoshi Jhono, Takaaki Ito, Nobuyuki Arima, Hironobu Ihn
  • Journal Title: The Journal of Dermatology Volume: 47(11) Issue: 11 Pages: 1317-1321
  • DOI: 10.1111/1346-8138.15543
  • Peer Reviewed
• [Journal Article] BATF2 expression as a novel marker for invasive phenotype in malignant melanoma (2020)
  • Author(s): Hidemi Tagawa, Hisashi Kanemaru, Toshihiro Kimura, Haruka Kuriyama, Soichiro Sawamura, Ikko Kajihara, Azusa Miyashita, Jun Aoi, Satoshi Fukushima, Hironobu Ihn
  • Journal Title: The Journal of Dermatology Volume: 47(10) Issue: 10 Pages: 372-373
  • DOI: 10.1111/1346-8138.15495
  • Peer Reviewed
• [Journal Article] Serum anti-p53 autoantibodies in angiosarcoma. (2020)
  • Author(s): Mihoko Kiyohara , Jun Aoi , Ikko Kajihara , Saki Otuka , Tuyoshi Kadomatsu , Satoshi Fukushima , Hironobu Ihn
  • Journal Title: Journal of Dermatology Volume: 47 Issue: 8 Pages: 849-854
  • DOI: 10.1111/1346-8138.15416
  • Peer Reviewed / Open Access
• [Journal Article] Induced pluripotent stem cell‐derived myeloid cells expressing OX40 ligand amplify antigen‐specific T cells in advanced melanoma (2020)
  • Author(s): Kimura Toshihiro、Fukushima Satoshi、Okada Etsuko、Miyashita Azusa、Tsukamoto Hirotake、Uemura Yasushi、Senju Satoru、Ihn Hironobu
  • Journal Title: Pigment Cell & Melanoma Research Volume: - Issue: 5 Pages: 744-755
  • DOI: 10.1111/pcmr.12887
  • Peer Reviewed / Open Access
• [Journal Article] Serious disseminated intravascular coagulation associated with combination therapy of nivolumab and ipilimumab in advanced melanoma. (2020)
  • Author(s): Kuriyama H, Fukushima S, Nakahara S, Kanemaru H, Miyashita A, Aoi J, Tomita Y, Kawasaki T, Nosaka K, Ihn H.
  • Journal Title: J Dermatol. Volume: - Issue: 6
  • DOI: 10.1111/1346-8138.15336
  • Peer Reviewed / Open Access
• [Journal Article] Case series of cutaneous T-cell lymphomas treated with bexarotene-based therapy (2020)
  • Author(s): Fujimura Taku、Sato Yota、Tanita Kayo、Amagai Ryo、Shimauchi Takatoshi、Ogata Dai、Fukushima Satoshi、Miyashita Azusa、Fujisawa Yasuhiro、Kambayashi Yumi、Aiba Setsuya
  • Journal Title: The Journal of Dermatology Volume: - Issue: 6 Pages: 636-640
  • DOI: 10.1111/1346-8138.15322
  • Peer Reviewed / Open Access
• [Journal Article] Inhibition of Endoglin Exerts Antitumor Effects through the Regulation of Non-Smad TGF-β Signaling in Angiosarcoma (2020)
  • Author(s): Ryoko Sakamoto, Ikko Kajihara, Hitomi Miyauchi, Saki Maeda-Otsuka, Saori Yamada-Kanazawa, Soichiro Sawamura, Hisashi Kanemaru, Katsunari Makino, Jun Aoi, Takamitsu Makino, Satoshi Fukushima, Mamiko Masuzawa, Mikio Masuzawa, Yasuyuki Amoh, Daichi Hoshina, Riichiro Abe, Hironobu Ihn
  • Journal Title: Journal of Investigative Dermatology Volume: － Issue: 10 Pages: 2060-2072.e6
  • DOI: 10.1016/j.jid.2020.01.031
  • Peer Reviewed
• [Journal Article] Successful treatment of occult pancreatic melanoma using BRAF/MEK inhibitors. (2020)
  • Author(s): Mizukami Y, Kanemaru H, Nakamura K, Hashigo S, Kajihara I, Miyashita A, Aoi J, Fukushima S, Honda Y, Ihn H.
  • Journal Title: J Dermatol. Volume: 47 Issue: 4
  • DOI: 10.1111/1346-8138.15198
  • Peer Reviewed / Open Access
• [Journal Article] Induced pluripotent stem cell-derived myeloid cells expressing OX40 ligand amplify antigen-specific T cells in advanced melanoma. (2020)
  • Author(s): Kimura T, Fukushima S, Okada E, Kuriyama H, Kanemaru H, Kadohisa-Tsuruta M, Kubo Y, Nakahara S, Tokuzumi A, Kajihara I, Makino K, Miyashita A, Aoi J, Makino T, Tsukamoto H, Nishimura Y, Inozume Y, Zhang R, Uemura Y, Senju S, Ihn H.
  • Journal Title: Pigment Cell & Melanoma Research. Volume: -
  • Peer Reviewed
• [Journal Article] Inhibition of Endoglin Exerts Antitumor Effects through the Regulation of Non-Smad TGF-β Signaling in Angiosarcoma. (2020)
  • Author(s): Sakamoto R, Kajihara I, Miyauchi H, Maeda-Otsuka S, Yamada-Kanazawa S, Sawamura S, Kanemaru H, Makino K, Aoi J, Makino T, Fukushima S, Masuzawa M, Masuzawa M, Amoh Y, Hoshina D, Abe R, Ihn H.
  • Journal Title: J Invest Dermatol. Volume: -
  • Peer Reviewed
• [Journal Article] MicroRNAs that predict the effectiveness of anti-PD-1 therapies in patients with advanced melanoma. (2020)
  • Author(s): Nakahara S, Fukushima S, Okada E, Morinaga J, Kubo Y, Tokuzumi A, Matsumoto S, Tsuruta-Kadohisa M, Kimura T, Kuriyama H, Miyashita A, Kajihara I, Jinnin M, Ihn H.
  • Journal Title: J Dermatol Sci. Volume: 97 Issue: 1 Pages: 77-79
  • DOI: 10.1016/j.jdermsci.2019.11.010
  • Peer Reviewed / Open Access
• [Journal Article] Effect of topical immunotherapy with squaric acid dibutylester for alopecia areata in Japanese patients (2020)
  • Author(s): Sakai K, Fukushima S, Mizuhashi S, Jinnin M, Makino T, Inoue Y, Ihn H.
  • Journal Title: Allergology International Volume: 69 Issue: 2 Pages: 274-278
  • DOI: 10.1016/j.alit.2019.10.008
  • NAID: 130007833061
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access
• [Journal Article] IL-16 expression is increased in the skin and sera of patients with systemic sclerosis. (2020)
  • Author(s): Kawabata K, Makino T, Makino K, Kajihara I, Fukushima S, Ihn H.
  • Journal Title: Rheumatology (Oxford). Volume: 59 Pages: 519-523
  • DOI: 10.1093/rheumatology/kez318
  • Peer Reviewed
• [Journal Article] Remarkable antitumor effect of nivolumab in a patient with metastatic renal cell carcinoma previously treated with a peptidebased vaccine. (2020)
  • Author(s): Kurahashi R, Motoshima T, Fukushima Y, Murakami Y, Yatsuda J, Yamaguchi T, Sugiyama Y, Fukushima S, Komohara Y, Suekane S, Tomomi Kamba T.
  • Journal Title: IJU Case Reports Volume: -
  • Peer Reviewed
• [Journal Article] Non-small-cell Lung Cancer with Severe Skin Manifestations Related to Radiation Recall Dermatitis after Atezolizumab Treatment: A Case Report. (2020)
  • Author(s): Nakashima K, Saruwatari K, Sato R, Imamura K, Kajihara I, Fukushima S, Saito T, Ishizuka S, Tamanoi D, Jodai T, Hamada S, Tomita Y, Saeki S, Ichiyasu H, Oya N, Ihn H, Sakagami T.
  • Journal Title: Intern Med. Volume: -
• [Journal Article] Onychomycosis caused by Trichosporon cacaoliposimilis. (2020)
  • Author(s): Noguchi H, Matsumoto T, Kimura U, Hiruma M, Kano R, Yaguchi T, Fukushima S, Ihn H.
  • Journal Title: J Dermatol. Volume: - Issue: 5
  • DOI: 10.1111/1346-8138.15305
  • Peer Reviewed
• [Journal Article] Case of metastatic extramammary Paget's disease treated with trastuzumab-biosimilar monotherapy after S-1 and docetaxel combination chemotherapy. (2020)
  • Author(s): Kimura T, Akamatsu Y, Kajihara I, Fukushima S, Ihn H. Ihn H.
  • Journal Title: J Dermatol. Volume: 47 Issue: 1
  • DOI: 10.1111/1346-8138.15096
  • Peer Reviewed
• [Journal Article] Cytomegalovirus Enterocolitis in a Patient with Refractory Immune-Related Colitis (2020)
  • Author(s): Furuta Y, Miyamoto H, Naoe H, Shimoda M, Hinokuma Y, Miyamura T, Miyashita A, Fukushima S, Tanaka M, Sasaki Y.
  • Journal Title: Case Rep Gastroenterol. Volume: 14 Issue: 1 Pages: 103-109
  • DOI: 10.1159/000506186
  • Peer Reviewed / Open Access
• [Journal Article] Royal jelly regulates the proliferation of human dermal microvascular endothelial cells through the down-regulation of a photoaging-related microRNA (2019)
  • Author(s): Kawano Y, Makino K, Jinnin M, Sawamura S, Shimada S, Fukushima S, Ihn H.
  • Journal Title: Drug Discoveries & Therapeutics Volume: 13 Issue: 5 Pages: 268-273
  • DOI: 10.5582/ddt.2019.01070
  • NAID: 130007744547
  • ISSN: 1881-7831, 1881-784X
  • Year and Date: 2019-10-31
  • Peer Reviewed / Open Access
• [Journal Article] A potential significance of circ_0024169 down regulation in angiosarcoma tissue (2019)
  • Author(s): Nakashima S, Jinnin M, Ide M, Kajihara I, Igata T, Harada M, Masuguchi S, Fukushima S, Masuzawa M, Masuzawa M, Amoh Y, Ihn H.
  • Journal Title: Intractable & Rare Diseases Research Volume: 8 Issue: 2 Pages: 129-133
  • DOI: 10.5582/irdr.2019.01034
  • NAID: 130007663175
  • ISSN: 2186-361X, 2186-3644
  • Year and Date: 2019-05-31
  • Peer Reviewed / Open Access
• [Journal Article] he Warburg effect and tumour immune microenvironment in extramammary Paget's disease: overexpression of lactate dehydrogenase A correlates with immune resistance. (2019)
  • Author(s): Urata K, Kajihara I, Miyauchi H, Mijiddorj T, Otsuka-Maeda S, Sakamoto R, Sawamura S, Kanemaru H, Kanazawa-Yamada S, Makino K, Aoi J, Makino T, Fukushima S, Komohara Y, Ihn H.
  • Journal Title: J Eur Acad Dermatol Venereol. Volume: - Issue: 8 Pages: 1715-1721
  • DOI: 10.1111/jdv.16145
  • Peer Reviewed
• [Journal Article] Japanese Dermatological Association Guidelines: Outlines of guidelines for cutaneous melanoma 2019. (2019)
  • Author(s): Nakamura Y, Asai J, Igaki H, Inozume T, Namikawa K, Hayashi A, Fukushima S, Fujimura T, Ito T, Imafuku K, Tanaka R, Teramoto Y, Minagawa A, Miyagawa T, Miyashita A, Wada M, Koga H, Sugaya M.
  • Journal Title: J Dermatol. Volume: 47 Issue: 2 Pages: 89-103
  • DOI: 10.1111/1346-8138.15151
  • Peer Reviewed / Open Access
• [Journal Article] Differential predictive factors for cardiovascular events in patients with or without cancer history. (2019)
  • Author(s): Sueta D, Tabata N, Ikeda S, Saito Y, Ozaki K, Sakata K, Matsumura T, Yamamoto-Ibusuki M, Murakami Y, Jodai T, Fukushima S, Yoshida N, Kamba T, Araki E, Iwase H, Fujii K, Ihn H, Kobayashi Y, Minamino T, Yamagishi M, Maemura K, Baba H, Matsui K, Tsujita K.
  • Journal Title: Medicine (Baltimore). Volume: 98 Issue: 44 Pages: e17602-e17602
  • DOI: 10.1097/md.0000000000017602
  • Peer Reviewed / Open Access
• [Journal Article] Dermatologic Oncology Group of the Japan Clinical Oncology Group. Confirmatory trial of non-amputative digit preservation surgery for subungual melanoma: Japan Clinical Oncology Group study (JCOG1602, J-NAIL study protocol). (2019)
  • Author(s): Tanaka K, Nakamura Y, Mizutani T, Shibata T, Tsutsumida A, Fukuda H, Matsushita S, Aoki M, Namikawa K, Ohe S, Fukushima S, Yamazaki N
  • Journal Title: BMC Cancer. Volume: 19 Issue: 1 Pages: 1002-1002
  • DOI: 10.1186/s12885-019-6248-2
  • Peer Reviewed / Open Access
• [Journal Article] Type I Interferon Delivery by iPSC-Derived Myeloid Cells Elicits Antitumor Immunity via XCR1+ Dendritic Cells. (2019)
  • Author(s): Tsuchiya N, Zhang R, Iwama T, Ueda N, Liu T, Tatsumi M, Sasaki Y, Shimoda R, Osako Y, Sawada Y, Kubo Y, Miyashita A, Fukushima S, Cheng Z, Nakaki R, Takubo K, Okada S, Kaneko S, Ihn H, Kaisho T, Nishimura Y, Senju S, Endo I, Nakatsura T, Uemura Y.
  • Journal Title: Cell Rep. Volume: 29 Issue: 1 Pages: 162-175
  • DOI: 10.1016/j.celrep.2019.08.086
  • Peer Reviewed / Open Access
• [Journal Article] Japanese real-world study of sequential nivolumab and ipilimumab treatment in melanoma. (2019)
  • Author(s): Tsutsumida A, Fukushima S, Yokota K, Yoshikawa S, Yamasaki O, Tanemura A, Okuyama R, Uhara H, Muto Y, Miyashita A, Akiyama M, Kaji T, Koga H, Kato J, Katayama T, Itakura E, Yamazaki N, Kiyohara Y.
  • Journal Title: J Dermatol. Volume: 46 Issue: 11 Pages: 947-955
  • DOI: 10.1111/1346-8138.15073
  • Peer Reviewed / Open Access
• [Journal Article] Classification of 3097 patients from the Japanese melanoma study database using the American joint committee on cancer eighth edition cancer staging system (2019)
  • Author(s): Fujisawa Y, ほか32名、 Katoh N（最終著者）
  • Journal Title: Journal of Dermatological Science Volume: 94 Issue: 2 Pages: 284-289
  • DOI: 10.1016/j.jdermsci.2019.04.003
  • Peer Reviewed
• [Journal Article] Clinical and histopathological characteristics and survival analysis of 4594 Japanese patients with melanoma (2019)
  • Author(s): Fujisawa Y, ほか32名、 Katoh N（最終著者）
  • Journal Title: Cancer Medicine Volume: 8 Issue: 5 Pages: 2146-2156
  • DOI: 10.1002/cam4.2110
  • Peer Reviewed / Open Access
• [Journal Article] Nivolumab‐induced colitis in a patient with malignant melanoma: A case report and immunological analysis (2019)
  • Author(s): Miyashita Azusa、Fukushima Satoshi、Tsukamoto Hirotake、Itai Hisae、Miyamoto Hideaki、Nakahara Satoshi、Kubo Yosuke、Kimura Toshihiro、Kuriyama Haruka、Ihn Hironobu
  • Journal Title: The Journal of Dermatology Volume: 0000 Issue: 9 Pages: 0000-0000
  • DOI: 10.1111/1346-8138.14857
  • Peer Reviewed / Open Access
• [Journal Article] Overexpression of cyclin-dependent kinase 4 protein in extramammary Paget's disease. (2019)
  • Author(s): Urata K, Kajihara I, Myangat TM, Tasaki Y, Otsuka-Maeda S, Sawamura S, Kanazawa-Yamada S, Sakamoto R, Makino K, Aoi J, Igata T, Makino T, Masuguchi S, Fukushima S, Jinnin M, Ihn H
  • Journal Title: The Journal of dermatology Volume: 印刷中 Issue: 5 Pages: 444-448
  • DOI: 10.1111/1346-8138.14858
  • Peer Reviewed
• [Journal Article] Serum cell-free DNA levels are a useful marker for extramammary Paget disease. (2019)
  • Author(s): Mijiddorj T, Kajihara I, Tasaki Y, Otsuka-Maeda S, Sakamoto R, Sawamura S, Kanazawa-Yamada S, Egashira S, Inoue K, Makino K, Miyashita A, Aoi J, Igata T, Makino T, Masuguchi S, Fukushima S, Jinnin M, Morinaga J, Ikeda T, Ihn H.
  • Journal Title: Br J Dermatol. Volume: 181 Issue: 3 Pages: 505-511
  • DOI: 10.1111/bjd.17709
  • Peer Reviewed / Open Access
• [Journal Article] Recurrent Fusion Gene ADCK4-NUMBL in Cutaneous Squamous Cell Carcinoma Mediates?Cell?Proliferation. (2019)
  • Author(s): Egashira S, Jinnin M, Makino K, Ajino M, Shimozono N, Okamoto S, Tazaki Y, Hirano A, Ide M, Kajihara I, Aoi J, Harada M, Igata T, Masuguchi S, Fukushima S, Ihn H
  • Journal Title: The Journal of investigative dermatology Volume: 139 Issue: 4 Pages: 954-957
  • DOI: 10.1016/j.jid.2018.09.030
  • Peer Reviewed / Open Access
• [Journal Article] Tinea unguium caused by terbinafine-resistant Trichophyton rubrum successfully treated with fosravuconazole. (2019)
  • Author(s): Noguchi H, Matsumoto T, Hiruma M, Kimura U, Kano R, Yaguchi T, Fukushima S, Ihn H.
  • Journal Title: J Dermatol. Volume: 46
  • Peer Reviewed
• [Journal Article] Fungal melanonychia caused by Candida parapsilosis successfully treated with oral fosravuconazole. (2019)
  • Author(s): Noguchi H, Matsumoto T, Kimura U, Hiruma M, Kano R, Yaguchi T, Fukushima S, Ihn H.
  • Journal Title: J Dermatol. Volume: 46 Issue: 10 Pages: 911-913
  • DOI: 10.1111/1346-8138.15024
  • Peer Reviewed
• [Journal Article] Interdigital Hyalohyphomycosis Caused by Members of the Fusarium solani Species Complex. (2019)
  • Author(s): Noguchi H, Matsumoto T, Hiruma M, Kimura U, Yaguchi T, Hirose M, Fukushima S, Ihn H.
  • Journal Title: Acta Derm Venereol. Volume: 99 Issue: 9 Pages: 835-836
  • DOI: 10.2340/00015555-3202
  • Peer Reviewed / Open Access
• [Journal Article] Natural course of epidermolysis bullosa simplex with mottled pigmentation in a Japanese family with the p.P25L mutation in KRT5. (2019)
  • Author(s): Okamura K, Fukushima S, Yamashita J, Abe Y, Hayashi M, Hozumi Y, Ihn H, Suzuki T
  • Journal Title: The Journal of dermatology Volume: 印刷中 Issue: 7
  • DOI: 10.1111/1346-8138.14788
  • Peer Reviewed
• [Journal Article] Case of cutaneous myoepithelioma managed with surgical resection without recurrence for 4?years. (2019)
  • Author(s): Kanemaru H, Honda N, Kubo Y, Nishihara H, Onuma T, Sakai K, Fukushima S, Inoue Y, Honda Y, Ihn H
  • Journal Title: The Journal of dermatology Volume: 印刷中 Issue: 6
  • DOI: 10.1111/1346-8138.14769
  • Peer Reviewed
• [Journal Article] Serum concentrations of HGF are correlated with response to anti-PD-1 antibody therapy in patients with metastatic melanoma. (2019)
  • Author(s): Kubo Y, Fukushima S, Inamori Y, Tsuruta M, Egashira S, Yamada-Kanazawa S, Nakahara S, Tokuzumi A, Miyashita A, Aoi J, Kajihara I, Tomita Y, Wakamatsu K, Jinnin M, Ihn H
  • Journal Title: Journal of dermatological science Volume: 93 Issue: 1 Pages: 33-10
  • DOI: 10.1016/j.jdermsci.2018.10.001
  • Peer Reviewed / Open Access
• [Journal Article] Onychomycosis caused by Aspergillus subramanianii. (2019)
  • Author(s): Hirose M, Noguchi H, Yaguchi T, Matsumoto T, Hiruma M, Fukushima S, Ihn H
  • Journal Title: The Journal of dermatology Volume: 45 Issue: 11 Pages: 1362-1366
  • DOI: 10.1111/1346-8138.14616
  • Peer Reviewed
• [Journal Article] Serum cytokine profiles are altered in patients with progressive infantile hemangioma (2018)
  • Author(s): Yamashita T, Jinnin M, Makino K, Kajihara I, Aoi J, Masuguchi S, Fukushima S, Ihn H
  • Journal Title: BioScience Trends Volume: 12 Issue: 4 Pages: 438-441
  • DOI: 10.5582/bst.2018.01118
  • NAID: 130007484789
  • ISSN: 1881-7815, 1881-7823
  • Year and Date: 2018-08-31
  • Peer Reviewed
• [Journal Article] Severe bacterial sepsis results in delayed diagnosis of tuberculous lymphadenitis in a rheumatoid arthritis patient treated with adalimumab (2018)
  • Author(s): Sawamura S, Makino T, Johno T, Yamashita J, Niimori D, Fukushima S, Ihn H
  • Journal Title: Intractable & Rare Diseases Research Volume: 7 Issue: 2 Pages: 138-140
  • DOI: 10.5582/irdr.2018.01050
  • NAID: 130007396053
  • ISSN: 2186-361X, 2186-3644
  • Year and Date: 2018-05-31
  • Peer Reviewed / Open Access
• [Journal Article] Reduction of stratum corneum ceramides in Neu-Laxova syndrome caused by phosphoglycerate dehydrogenase deficiency. (2018)
  • Author(s): Reduction of stratum corneum ceramides in Neu-Laxova syndrome caused by phosphoglycerate dehydrogenase deficiency.
  • Journal Title: Journal of lipid research Volume: 59 Issue: 12 Pages: 2413-1420
  • DOI: 10.1194/jlr.p087536
  • Peer Reviewed
• [Journal Article] Immune checkpoint inhibitors in the onset of myasthenia gravis with hyperCKemia. (2018)
  • Author(s): Koutaro Takamatsu, Shunya Nakane, Shigeaki Suzuki, Takayuki Kosaka, Satoshi Fukushima, Toshihiro Kimura, Azusa Miyashita, Akihiro Mukaino, Shiori Yamakawa, Keisuke Watanabe, Masatoshi Jinnin, Yoshihiro Komohara, Hironobu Ihn, and Yukio Ando
  • Journal Title: Ann Clin Transl Neurol. Volume: 5 Issue: 11 Pages: 1421-1427
  • DOI: 10.1002/acn3.654
  • Peer Reviewed / Open Access
• [Journal Article] Topical efinaconazole: A promising therapeutic medication for tinea unguium. (2018)
  • Author(s): Noguchi H, Matsumoto T, Hiruma M, Asao K, Hirose M, Fukushima S, Ihn H
  • Journal Title: The Journal of dermatology Volume: 45 Issue: 10 Pages: 1225-1228
  • DOI: 10.1111/1346-8138.14575
  • Peer Reviewed
• [Journal Article] Regulatory mechanisms of collagen expression by interleukin-22 signaling in scleroderma fibroblasts (2018)
  • Author(s): Sawamura Soichiro、Jinnin Masatoshi、Inoue Kuniko、Yamane Keitaro、Honda Noritoshi、Kajihara Ikko、Makino Takamitsu、Masuguchi Shinichi、Fukushima Satoshi、Ihn Hironobu
  • Journal Title: J Dermatol Sci. Volume: 90 Issue: 1 Pages: 52-59
  • DOI: 10.1016/j.jdermsci.2017.12.017
  • Peer Reviewed
• [Journal Article] Combined Blockade of IL6 and PD-1/PD-L1 Signaling Abrogates Mutual Regulation of Their Immunosuppressive Effects in the Tumor Microenvironment (2018)
  • Author(s): Tsukamoto Hirotake、Fujieda Koji、Miyashita Azusa、Fukushima Satoshi、Ikeda Tokunori、Kubo Yosuke、Senju Satoru、Ihn Hironobu、Nishimura Yasuharu、Oshiumi Hiroyuki
  • Journal Title: Cancer Research Volume: 78 Issue: 17 Pages: 5011-5022
  • DOI: 10.1158/0008-5472.can-18-0118
  • Peer Reviewed / Open Access
• [Journal Article] Dabrafenib and trametinib combination therapy safely performed in a patient with metastatic melanoma after severe liver toxicity due to vemurafenib. (2018)
  • Author(s): Shimada S, Fukushima S, Niimori D, Miyashita A, Setoyama H, Sasaki Y, Ihn H.
  • Journal Title: The Journal of Dermatology Volume: 0 Issue: 6 Pages: 0-0
  • DOI: 10.1111/1346-8138.14206
  • Peer Reviewed / Open Access
• [Journal Article] Simple and effective modification of the axial frontonasal flap to prevent flap distortion. (2018)
  • Author(s): Aoi J, Kajihara I, Masuguchi S, Fukushima S, Ihn H
  • Journal Title: The Journal of dermatology Volume: 46 Issue: 1 Pages: 46-47
  • DOI: 10.1111/1346-8138.14506
  • Peer Reviewed
• [Journal Article] 免疫チェックポイント阻害薬による副作用とその対策 (2018)
  • Author(s): 福島聡
  • Journal Title: Vita Volume: 35 Pages: 64-70
• [Presentation] 1.Efficacy of salvage therapies after failure of anti-PD-1 monotherapy for advanced melanoma in an Asian population: A multi-institutional historical cohort study (2020)
  • Author(s): Y Teramoto, K Namikawa, Y Kiniwa, K Yoshino, S Yoshikawa, Y Nakamura, T Funakoshi, T Takenouchi, T Isei, T Maekawa, T Miyagawa, Y Fujisawa, K Yokota, T Ito, H Uhara, S Matsushita, H Doi, Y Shibayama, S Fukushima, N Yamazaki
  • Organizer: The European Society for Medical Oncology (ESMO) Virtual Congress 2020
  • Int'l Joint Research
• [Presentation] 3.Real-world efficacy of anti-PD-1 antibodies in advanced subungual melanoma: The large multicenter retrospective Japanese Acral Melanoma PD-1 (JAMP) study of 70 cases (2020)
  • Author(s): Y Nakamura, K Namikawa, K Yoshino, S Yoshikawa, H Uchi, K Goto, Y Nakamura, S Fukushima, Y Kiniwa, T Takenouchi, H Uhara, T Kawai, N Hatta, T Funakoshi, Y Teramoto, A Otsuka, J Uehara, D Ogata, S Matsushita, N Yamazaki
  • Organizer: 16TH European Association of Dermato-Oncology Congress
  • Int'l Joint Research
• [Presentation] 免疫チェックポイント阻害薬による免疫関連有害事象に対するiREACT 活動の評価 (2020)
  • Author(s): 成田さわな・久本佳奈・冨田雄介・宮本英明・吉永 佳代・森永潤・山ノ内祥訓・佐伯祥・陶山浩一・福島聡
  • Organizer: 第41回臨床薬理学会
• [Presentation] Combination of anti-IL-6 and anti-PD-L1 antibodies synergistically induced a potent cancer immunity by activating both CTL and Th1 cells in mice. (2019)
  • Author(s): Nishimura Y, Fujieda K, Miyashita A, Fukushima S, Ikeda T, Kubo Y, Senju S, Ihn H, Oshiumi H, Tsukamoto H.
  • Organizer: AACR (American Association for Cancer Research)
  • Int'l Joint Research
• [Presentation] 腫瘍免疫の先駆け、メラノーマ (2018)
  • Author(s): 福島聡
  • Organizer: 第46回日本臨床免疫学会総会
• [Presentation] 皮膚悪性腫瘍の新しい生物学的製剤 (2018)
  • Author(s): 福島聡
  • Organizer: 第117回日本皮膚科学会総会
• [Presentation] 血清可溶性PD-L1濃度のメラノーマ患者における検討 (2018)
  • Author(s): 福島聡、稲森有貴子、久保陽介、中原智史、宮下梓、鶴田美菜、徳澄亜紀、新森大佑、熊井良彦、高村晴香、折田頼尚、尹浩信
  • Organizer: 第22回日本がん免疫学会総会
• [Presentation] Serum levels of soluble programmed death-ligand 1 in patients with metastatic melanoma (2018)
  • Author(s): Satoshi FUKUSHIMA, Yukiko INAMORI, Yosuke KUBO, Satoshi NAKAHARA, Azusa MIYASHITA, Mina TSURUTA, Aki TOKUZUMI, Daisuke NIIMORI, Ikko KAJIHARA, Masatoshi JINNIN, Hironobu IHN1
  • Organizer: 第77回日本癌学会学術総会
• [Presentation] Serum levels of soluble programmed death-ligand 1 in patients with metastatic melanoma treated with anti-programmed death-1 antibodies (2018)
  • Author(s): S. FUKUSHIMA, Y. INAMORI, Y. KUBO S. NAKAHARA, A. MIYASHITA, M. KADOHISA, A. TOKUZUMI, D. NIIMORI, S. MASUGUCHI, M. JINNIN, H. IHN
  • Organizer: 13th Meeting of the German-Japanese Society for Dermatology