Development of a new cancer immunotherapy with dendritic cells and macrophages by IL-27

2013 Fiscal Year Final Research Report

• Project/Area Number: 24659595
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: General surgery
• Research Institution: Tokyo Medical University
• Principal Investigator: HISADA Masayuki 東京医科大学, 医学部, 講師 (50385100)
• Co-Investigator(Kenkyū-buntansha): TSUCHIDA Akihiko 東京医科大学, 医学部, 教授 (50207396) ; YOSHIMOTO Takayuki 東京医科大学, 医学部, 教授 (80202406)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: IL-27 / 抗腫瘍効果 / 樹状細胞

Research Abstract

In the present study, we have elucidated following three new things aiming at application for cancer immunotherapy with IL-27; (1) IL-27 together with LPS augments nitric oxide production in macrophages through STAT1/NF-kB/MAPKs, (2) IL-27 enhances the expression of TRAIL and TLR3 in tumors through STAT1/IRF-1 and inhibits their tumor growth in cooperation with poly(I:C), partly in a TRAIL-dependent manner, (3) dendritic cells generated from myeloid progenitor cells differentiated and expanded by IL-27 and SCF can be potentially applied for dendritic-based therapeutic cancer vaccines.

Research Products

• [Journal Article] Intratumoral CD4^+ T lymphodepletion sensitizes poorly immunogenic melanomas to immunotherapy with an OX40 agonist (2014)
  • Author(s): Fujiwara S, Nagai H, Shimoura N, Oniki S, Yoshimoto T, Nishigori C
  • Journal Title: J. Invest. Dermatol
  • DOI: 10.1038/jid.2014.42
  • Peer Reviewed
• [Journal Article] Examination of prognostic factors in patients undergoing surgery for colorectal perforation : A case controlled study (2014)
  • Author(s): Sumi T, Katsumata K, Katayanagi S, Nakamura Y, Nomura T, Takano K, Kasuya K, Shimadzu M, Tsuchida A
  • Journal Title: Int J Surg
  • DOI: 10.1016/j.ijsu.2014.03.021
  • Peer Reviewed
• [Journal Article] Usefulness of multi-3-dimensional computed tomograms fused with multiplanar reconstruction images and peroral cholangioscopy findings in hilar cholangiocarcinoma (2014)
  • Author(s): Nagakawa Y, Kasuya K, Bunso K, Hosokawa Y, Kuwabara H, Nakagima T, Osakabe H, Tsuchiya T, Itoi T, Tsuchida A
  • Journal Title: J Hepatobiliary Pancreat Sci Volume: 21(4) Pages: 256-62
  • Peer Reviewed
• [Journal Article] Relationship between the liver tissue shear modulus and histopathologic findings analyzed by intraoperative shear wave elastography and digital microscopically assisted morphometry in patients with hepatocellular carcinoma (2014)
  • Author(s): Honjo M, Moriyasu F, Sugimoto K, Oshiro H, Sakamaki K, Kasuya K, Nagai T, Tsuchida A, Imai Y
  • Journal Title: J Ultrasound Med Volume: 33(1) Pages: 61-71
  • Peer Reviewed
• [Journal Article] MicroRNA-18a modulates STAT3 activity through negative regulation of PIAS3 during gastric adenocarcinogenesis (2013)
  • Author(s): Wu W, Takanashi M, Borjigin N, Ohno SI, Fujita K, Hoshino S, Osaka Y, Tsuchida A, Kuroda M
  • Journal Title: Br J Cancer Volume: 108(3) Pages: 653-61
  • Peer Reviewed
• [Journal Article] Bacterial contamination in ascitic fluid is associated with the development of clinically relevant pancreatic fistula after pancreatoduodenectomy (2013)
  • Author(s): Nagakawa Y, Matsudo T, Hijikata Y, Kikuchi S, Bunso K, Suzuki Y, Kasuya K, Tsuchida A
  • Journal Title: Pancreas Volume: 42(4) Pages: 701-6
  • Peer Reviewed
• [Journal Article] Pivotal roles of T-helper 17-related cytokines, IL-17, IL-22 and IL-23, in inflammatory diseases (2013)
  • Author(s): Qu N, Xu M, Mizoguchi I, Furusawa J, Kaneko K, Watanebe K, Mizuguchi J, Itoh M, Kawakami Y, Yoshimoto T
  • Journal Title: Clin. Dev. Immunol Volume: 2013 Pages: 968549
  • DOI: 10.1155/2013/968549
  • Peer Reviewed
• [Journal Article] IL-27 enhances the expression of TRAIL and TLR3 in human melanomas and inhibits their tumor growth in cooperating with a TLR3 agonist poly(I : C) partly in TRAIL-dependent manner (2013)
  • Author(s): Chiba Y, Mizoguchi K, Mitobe I, Higuchi K, Nagai H, Nishigori C, Mizuguchi J, Yoshimoto T
  • Journal Title: PLoS One Volume: 8(10) Pages: e76159
  • DOI: 10.1371/journal.pone.0076159
  • Peer Reviewed
• [Journal Article] Sustained up-regulation of effector natural killer cells in chronic myeloid leukemia after discontinuation of imatinib (2013)
  • Author(s): Mizoguchi I, Yoshimoto T, Katagiri S, Mizuguchi J, Tauchi T, Kimura Y, Inokuchi K, Ohyashiki JH, Ohyashiki K
  • Journal Title: Cancer Sci Volume: 104 Pages: 1146-1153
  • Peer Reviewed
• [Journal Article] The ARNT-Stat3 axis regulates the differentiation of intestinal intraepithelial TCRαβ^+CD8αα^+ cells (2013)
  • Author(s): Nakajima K, Maekawa Y, Kataoka K, Ishifune C, Nishida J, Arimochi H, Kitamura A, Yoshimoto T, Tomita S, Nagahiro S, Yasutomo K
  • Journal Title: Nat. Commun Volume: 4 Pages: 2112
  • DOI: 10.1038/ncomms3112
  • Peer Reviewed
• [Journal Article] IL-27 promotes nitric oxide production induced by LPS through STAT1, NF-κB and MAPKs (2013)
  • Author(s): Shimizu M, Ogura K, Mizoguchi I, Chiba Y, Higuchi K, Ohtsuka H, Mizuguchi J, Yoshimoto T
  • Journal Title: Immunobiology Volume: 218 Pages: 628-634
  • Peer Reviewed
• [Journal Article] Identification of a novel role of septin 10 in paclitaxel-resistance in cancers through a functional genomics screen (2012)
  • Author(s): Xu M, Takanashi M, Oikawa K, Nishi H, Isaka K, Yoshimoto T, Ohyashiki J, Kuroda M
  • Journal Title: Cancer Sci Volume: 103(4) Pages: 821-827
  • Peer Reviewed
• [Journal Article] Epithelial cell-derived IL-25, but not Th17 cell-derived IL-17 or IL-17F, is crucial for murine asthma (2012)
  • Author(s): Suzukawa M, Morita H, Nambu A, Arae K, Shimura E, Shibui A, Yamaguchi S, Suzukawa K, Nakanishi W, Oboki K, Kajiwara N, Ohno T, Ishii A, Korner H, Cua DJ, Suto H, Yoshimoto T, Iwakura Y, Yamasoba T, Ohta K, Sudo K, Saito H, Okumura K, Broide DH, Matsumoto K, Nakae S
  • Journal Title: J Immunol Volume: 189(7) Pages: 3641-3652
  • Peer Reviewed
• [Journal Article] 劇症型A群溶連菌感染症(TSLS)を呈した骨盤腹膜炎の1例 (2012)
  • Author(s): 久田将之、河北英明、石崎哲央、井上敬一郎、土田明彦、青木達哉
  • Journal Title: 日本外科系連合学会誌 Volume: 37(4) Pages: 869-75
• [Journal Article] 術前診断しえた侵襲性血管粘膜嚢腫の1例 (2012)
  • Author(s): 久田将之、勝又健次、河北英明、石崎哲央、高木融、土田明彦、青木達哉、佐藤栄一
  • Journal Title: 日本外科系連合学会誌 Volume: 37(6) Pages: 1147-52
• [Journal Article] 下部消化管のrobotic surgery (2012)
  • Author(s): 久田将之、和田建彦、土田明彦、青木達哉
  • Journal Title: 臨床雑誌「外科」 Volume: 74(8)別 Pages: 829-33
• [Journal Article] サイトカインのすべてIL-27 (2012)
  • Author(s): 千葉祐規乃、溝口出、森嶋紀子、徐明利、善本隆之
  • Journal Title: 臨床免疫・アレルギー科 Volume: 57 (Suppl. 21) Pages: 172-183
• [Journal Article] DCワクチンをリンパ節投与した際の局所滞留性と免疫誘導能の検討 (2012)
  • Author(s): 太田裕士、徐明利、溝口出、高梨正勝、須藤カツ子、黒田雅彦、善本隆之、粕谷和彦、土田明彦、畝崎栄
  • Journal Title: 東京医科大学雑誌 Volume: 70(4) Pages: 444-449
  • Peer Reviewed
• [Journal Article] Combination therapy of gemcitabine or oral S-1 with the anti-VEGF monoclonal antibody bevacizumab for pancreatic neuroendocrine carcinoma (2012)
  • Author(s): Kasuya K, Nagakawa Y, Suzuki M, Suzuki Y, Kyo B, Suzuki S, Matsudo T, Itoi T, Tsuchida A, Aoki T
  • Journal Title: Exp Ther Med Volume: 3(4) Pages: 599-602
  • Peer Reviewed
• [Journal Article] Administration of anti-vascular endothelial growth factor antibody following hepatectomy does not inhibit remnant liver regeneration or growth of remnant metastases (2012)
  • Author(s): Kasuya K, Suzuki M, Nagakawa Y, Suzuki Y, Kikuchi S, Kyo B, Matsudo T, Itoi T, Tsuchida A, Aoki T
  • Journal Title: Exp Ther Med Volume: 3(2) Pages: 347-350
  • Peer Reviewed
• [Journal Article] Computed tomography virtual endoscopy with angiographic imaging for the treatment of type IV-A choledochal cyst (2012)
  • Author(s): Tsuchida A, Nagakawa Y, Kasuya K, Kyo B, Ikeda T, Suzuki Y, Aoki T, Itoi T
  • Journal Title: World J Gastroenterol Volume: 18(28) Pages: 3761-4
  • Peer Reviewed
• [Journal Article] Comparison of preoperative images with gross and histopathological findings of liver slices in patients with liver metastases from colorectal cancer after chemotherapy (2012)
  • Author(s): Kasuya K, Oshiro H, Saito K, Suzuki Y, Kikuchi S, Kyo B, Matsudo T, Nagakawa Y, Itoi T, Tsuchida A
  • Journal Title: Hepatogastroenterology Volume: 59(116) Pages: 981-5
  • Peer Reviewed
• [Presentation] IL-27 promotes the differentiation of bone marrow cells into DC progenitor cells (2013)
  • Author(s): Furusawa, J., Mizoguchi, I., Mizuguchi, J., and Yoshimoto, T
  • Organizer: 第42回日本免疫学会総会
  • Place of Presentation: 幕張
  • Year and Date: 20131211-13
• [Presentation] Long-term up-regulation of effector NK cells in CML after stopping imatinib (2013)
  • Author(s): Katagiri, S., Mizoguchi, I., Yoshimoto, T., Ohyashiki, J.H., Tauchi, T., Inokuchi, K., and Ohyashiki, K
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 20131011-13
• [Presentation] New approach for DC-mediated cancer vaccine using IL-27-expanded myeloid progenitor cells (2013)
  • Author(s): Yoshimoto, T., Mizoguchi, I. Hisada, M., and Mizuguchi, J
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 20131003-05
• [Presentation] サイトカインによる免疫制御法 The percentage of effector populations of NK cells correlated highly with sustained CMR with or without imatinib in chronic myeloid leukemia patients (2013)
  • Author(s): 善本隆之, Katagiri, S., Mizoguchi, I., Yoshimoto, T., Mizuguchi, J., Ohyashiki, J.H., Tauchi, T., Inokuchi, K., and Ohyashiki, K
  • Organizer: 18th Congress of the European Hematology Association
  • Place of Presentation: Stockholm, Sweden
  • Year and Date: 20130613-16
• [Presentation] 癌DCワクチン療法への応用を目指したIL-27を用いたDC前駆細胞の分化・増殖誘導法の開発 (2013)
  • Author(s): 古津純一、溝口出、水戸部佳奈、樋口要、金子幸太郎、角田廉、水口純一郎、久田将之、粕谷和彦、土田明彦、善本隆之
  • Organizer: 医薬工3大学包括的連携推進シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2013-12-14
• [Presentation] IL-6/IL-12ファミリーサイトカインIL-27によるDC前駆細胞の分化・増殖誘導 (2013)
  • Author(s): 古津純一、水戸部佳奈、溝口出、金子幸太郎、角田廉、樋口要、善本隆之
  • Organizer: 東京医科大学記念館ポスター発表懇談会
  • Place of Presentation: 東京
  • Year and Date: 2013-11-28
• [Presentation] IL-27によるDC前駆細胞の分化・増殖誘導 (2013)
  • Author(s): 古津純一、溝口出、水戸部佳奈、樋口要、金子幸太郎、角田廉、水口純一郎、久田将之、粕谷和彦、土田明彦、善本隆之
  • Organizer: 第90回東京医科大学・東京薬科大学・免疫アレルギー研究会
  • Place of Presentation: 東京
  • Year and Date: 2013-11-05
• [Presentation] Activation levels of natural killer cells and CD8^+ T cells correlate highly with sustained complete molecular response after discontinuation of imatinib in chronic myeloid leukemia patients (2012)
  • Author(s): Katagiri, S., Mizoguchi, I., Yoshimoto, T., Mizuguchi, J., Ohyashiki, J.H., and Ohyashiki, K
  • Organizer: 2012 ASH Annual Meeting and Exposition
  • Place of Presentation: Atlanta GA, USA
  • Year and Date: 20121208-11
• [Presentation] Induction of nitric oxide by macrophages stimulated with IL-27 and lipopolysaccaride through STAT1, NF-kB and MAPKs (2012)
  • Author(s): Shimizu, M., Mizoguchi, I., Mizuguchi, J., and Yoshimoto, T
  • Organizer: 第41回日本免疫学会総会
  • Place of Presentation: 神戸
  • Year and Date: 20121205-07
• [Presentation] Comparison of antigen-loading methods into dendritic cells with protein, mRNA or peptides derived ovalbumin for antigen presenting activity (2012)
  • Author(s): Nagaoka, K., Miki, K., Yoshimoto, T., Kamigaki, T., and Maekawa, R
  • Organizer: The 12^<th> International Symposium on Dendritic Cells
  • Place of Presentation: Daegu, Korea
  • Year and Date: 20121007-11
• [Presentation] Activation levels of NK and CD8^+ T cells correlate with sustained CMR after discontinuation of imatinib in CML patients (2012)
  • Author(s): Yoshimoto, T., Mizoguchi, I., Katagiri, S., Mizuguchi, J., Ohyashiki, J., and Ohyashiki, K
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 20120919-21
• [Presentation] Cooperative growth inhibition of human melanomas by IL-27 and a TLR3 agonist poly(I : C) in TRAIL-dependent manner (2012)
  • Author(s): Mizoguchi, I., Mizuguchi, J., and Yoshimoto, T
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 20120919-21
• [Presentation] Dendritic cells loaded with antigen by electroporation induce strong anti-tumor immunity in vivo (2012)
  • Author(s): Nagaoka, K., Miki, K., Yoshimoto, T., Teruya, T., Shiroma, H., and Maekawa, R
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 20120919-21
• [Presentation] Efficient antigen presentation and induction of anti-tumor immunity by dendritic cells loaded with antigens by electroporation (2012)
  • Author(s): Nagaoka, K., Takahara,M., Yoshimoto, T., Teruya, T., Shiroma, H., and Maekawa, R
  • Organizer: American Association of Cancer (AACR) Annual Meeting 2012
  • Place of Presentation: Chicago, IL, USA
  • Year and Date: 20120331-0404
• [Presentation] DCワクチンをリンパ節投与した際の局所滞留性と免疫誘導能の検討 (2012)
  • Author(s): 太田裕士、徐明利、溝口出、高梨正勝、須藤カツ子、黒田雅彦、善本隆之、粕谷和彦、土田明彦、畝崎栄
  • Organizer: 第132年会日本薬学会
  • Place of Presentation: 札幌
  • Year and Date: 20120328-31
• [Presentation] 腹腔鏡下手術と手術支援ロボットDavinciをハイブリッドさせて完全腹腔鏡下前方切除術 (2012)
  • Author(s): 久田将之、石崎哲央、林田康治、楢崎克典、河北英明、勝又健次、土田明彦
  • Organizer: 第25回日本内視鏡外科学会総会
  • Place of Presentation: 神奈川
  • Year and Date: 2012-12-08
• [Presentation] 当科における経工門的引抜き法による完全腹腔鏡下前方切除術を行った3例 (2012)
  • Author(s): 久田将之、石崎哲央、林田康治、楢崎克典、勝又健次、高木融、土田明彦
  • Organizer: 第74回日本臨床外科学会総会
  • Place of Presentation: 東京
  • Year and Date: 2012-11-29
• [Presentation] 当科における完全腹腔鏡下前方切除術 (2012)
  • Author(s): 久田将之、和田建彦、石崎哲央、河北英明、村越雄介、土田明彦、青木達哉
  • Organizer: 第67回日本消化器外科学会
  • Place of Presentation: 富山
  • Year and Date: 2012-07-18
• [Presentation] ロボット支援手術Davinciを用いた完全腹腔鏡下前方切除術と吻合方の工夫 (2012)
  • Author(s): 久田将之、和田建彦、石崎哲央、河北英明、村越雄介、土田明彦、青木達哉
  • Organizer: 第37回外科系連合学会
  • Place of Presentation: 九州
  • Year and Date: 2012-06-29
• [Presentation] Trial of total laparoscopic low anterior resection (2012)
  • Author(s): Hisada, M., Wada, T., Ishizaki, T., Kawakita, H., Tsuchida, A., and Aoki, T
  • Organizer: XXV ISUCRS Biennial Congress
  • Place of Presentation: Bologna, Italy
  • Year and Date: 2012-06-26
• [Presentation] エレクトロポレーション法で抗原導入した樹状細胞は高い抗原提示能を有し、生体内投与により高い抗腫療効果を示す (2012)
  • Author(s): 長岡孝治、高原将司、三木健次、善本隆之、照屋剛、城間寛、神垣隆、前川隆司
  • Organizer: 第22回日本樹状細胞研究会
  • Place of Presentation: 福島
  • Year and Date: 2012-06-15
• [Presentation] IL-27とPoly(I : C)による協調的TRAILとTLR3発現増強を介したメラノーマ腫療増殖のTRAIL依存的抑制 (2012)
  • Author(s): 溝口出、千葉祐規乃、徐明利、樋口要、水口純一郎、善本隆之
  • Organizer: 第87回東京医科大学・東京薬科大学・免疫アレルギー研究会
  • Place of Presentation: 東京
  • Year and Date: 2012-05-29
• [Presentation] 当科における大腸癌レイウスの治療成績と方針 (2012)
  • Author(s): 久田将之、和田建彦、石崎哲央、河北英明、村越雄介、土田明彦、青木達哉
  • Organizer: 第48回日本腹部救急医学学会総会
  • Place of Presentation: 金沢
  • Year and Date: 2012-03-15