悪性神経膠腫療法時の免疫応答とheterogeneityの関係
Project/Area Number |
19K09457
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 56010:Neurosurgery-related
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Research Institution | Osaka University |
Principal Investigator |
香川 尚己 大阪大学, 大学院医学系研究科, 講師 (50444542)
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Co-Investigator(Kenkyū-buntansha) |
坪井 昭博 大阪大学, 大学院医学系研究科, 招へい教授 (10372608)
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Project Period (FY) |
2019-04-01 – 2024-03-31
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Project Status |
Completed (Fiscal Year 2023)
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Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | 悪性神経膠腫 / 免疫応答 / heterogeneity / 腫瘍幹細胞 / 腫瘍血管正常化 |
Outline of Research at the Start |
神経膠腫のゲノム・エピゲノムを含むheterogeneityと免疫応答の関係性を明らかにするとともに、腫瘍幹細胞や微小環境による腫瘍免疫抑制の解明、免疫療法と新生血管抑制因子を含む分子標的薬との組み合わせやタイミングなどを検討する基礎的な研究を模索することにより、我が国発信の免疫療法を含んだ新たな臨床試験の可能性が広がり、治療成績を改善させる礎となることを期待する。
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Outline of Annual Research Achievements |
我々の研究室では、WT1を中心とする免疫療法を悪性神経膠腫に対して導入し、治療反応性に関する研究や免疫逃避現象に関する研究を行ってきた。腫瘍抵抗性の原因として、腫瘍幹細胞の治療抵抗性とその制御、腫瘍血管正常化による治療効果について研究を進めてきた。また同時に、大規模な遺伝子解析の知見が急速に進み、分子分類による予後予測などが可能となってきている反面、腫瘍細胞の多様性・不均一性が問題となっている。クローン進化やエピゲノム変化などの内的要因に、微小環境や相互作用などの外的要因が加わり、多彩な治療反応性が作り出されると考えられる。また、免疫療法終了後に神経血管抑制薬を投与した症例やその反対の順序での薬剤投与に関して、現時点で免疫応答を予測するデータは存在しない。 神経膠腫のゲノム・エピゲノムを含むheterogeneityと免疫応答の関係性を明らかにするとともに、腫瘍幹細胞や微小環境による腫瘍免疫抑制の解明、免疫療法と新生血管抑制因子を含む分子標的薬との組み合わせやタイミングなどを検討する基礎的な研究を模索することにより、我が国発信の免疫療法を含んだ新たな臨床試験の可能性が広がり、治療成績を改善させる礎となることを期待する。 本研究では、悪性神経膠腫における腫瘍幹細胞の免疫抑制特性を確認し、治療抵抗性を生じる機構を解明し、免疫療法と血管正常化因子(新生血管抑制)の効果を様々な組み合わせで検証する実験を行った。また、腫瘍細胞のゲノム・エピゲノムと免疫応答の関係性、腫瘍のheterogeneityとの関係性を探ることにより、治療反応への影響を解明し、治療抵抗性、免疫逃避現象機構を明らかにした。さらに、より横断的な悪性神経膠腫の診断と新しい分類への試みへの応用も模索した。
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Report
(5 results)
Research Products
(60 results)
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[Journal Article] WT1 Trio Peptide-Based Cancer Vaccine for Rare Cancers Expressing Shared Target WT12023
Author(s)
Oji Y, Kagawa N, Arita H, Naka N, Hamada KI, Outani H, Shintani Y, Takeda Y, Morii E, Shimazu K, Suzuki M, Nishida S, Nakata J, Tsuboi A, Iwai M, Hayashi S, Imanishi R, Ikejima S, Kanegae M, Iwamoto M, Ikeda M, Yagi K, Shimokado H, Nakajima H, Hasegawa K, Morimoto S, Fujiki F 他
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Journal Title
Cancers
Volume: 15
Issue: 2
Pages: 393-393
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[Journal Article] Subtyping of Group 3/4 medulloblastoma as a potential prognostic biomarker among patients treated with reduced dose of craniospinal irradiation: a Japanese Pediatric Molecular Neuro-Oncology Group study.2023
Author(s)
Fukuoka K, Kurihara J, Shofuda T, Kagawa N, Yamasaki K, Ando R, Ishida J, Kanamori M, Kawamura A, Park YS, Kiyotani C, Akai T, Keino D, Miyairi Y, Sasaki A, Hirato J, Inoue T, Nakazawa A, Koh K, Nishikawa R, Date I, Nagane M, Ichimura K, Kanemura Y
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Journal Title
Acta Neuropathol Commun.
Volume: 11(1)
Issue: 1
Pages: 153-153
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[Journal Article] Successful separation of male pygopagus with anal canal and urethral reconstruction: a case report2022
Author(s)
Toyama C, Nomura M, Tazuke Y, Yokota C, Kagawa N, Kishima H, Yoshimura A, Ujike T, Nagahara A, Nonomura N, Kubo T, Matsui F, Matsumoto F, Okuyama H.
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Journal Title
Surg Case Rep.
Volume: 8(1)
Issue: 1
Pages: 43-43
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Peer Reviewed / Open Access
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[Journal Article] Cerebellopontine angle metastasis of a neuroendocrine tumor mimicking vestibular schwannoma: A case report.2022
Author(s)
Yamada S, Kijima N†, Kinoshita M, Shinzaki S, Sato K, Kido K, Hirayama R, Kagawa N, Takehara T, Morii E, Kishima H.
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Journal Title
Surgical Neurology International
Volume: 13
Pages: 264-264
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[Journal Article] Growth risk classification and typical growth speed of convexity, parasagittal, and falx meningiomas: a retrospective cohort study2022
Author(s)
Yamada S, Hirayama R, Iwata T, Kuroda H, Nakagawa T, Takenaka T, Kijima N, Okita Y, Kagawa N, Kishima H.
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Journal Title
J Neurosurg.
Volume: 138(5)
Issue: 5
Pages: 1235-1241
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[Journal Article] Revisiting the definition of glioma recurrence based on a phylogenetic investigation of primary and re-emerging tumor samples: a case report2022
Author(s)
Umehara T, Arita H, Miya F, Achiha T, Shofuda T, Yoshioka E, Kanematsu D, Nakagawa T, Kinoshita M, Kagawa N, Fujimoto Y, Hashimoto N, Kiyokawa H, Morii E, Tsunoda T, Kanemura Y, Kishima H.
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Journal Title
Brain Tumor Pathol.
Volume: 39(4)
Issue: 4
Pages: 218-224
DOI
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Peer Reviewed / Open Access
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[Journal Article] Identification of glioblastoma-specific antigens expressed in patient-derived tumor cells as candidate targets for chimeric antigen receptor T cell therapy2022
Author(s)
Nakagawa T, Kijima N, Hasegawa K, Ikeda S, Yaga M, Wibowo T, Tachi T, Kuroda H, Hirayama R, Okita Y, Kinoshita M, Kagawa N, Kanemura Y, Hosen N, Kishima H.
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Journal Title
Neurooncol Adv.
Volume: 5(1)
Issue: 1
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Peer Reviewed / Open Access
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[Journal Article] Efficacy and safety of nivolumab in Japanese patients with first recurrence of glioblastoma: an open-label, non-comparative study.2021
Author(s)
Aoki T, Kagawa N, Sugiyama K, Wakabayashi T, Arakawa Y, Yamaguchi S, Tanaka S, Ishikawa E, Muragaki Y, Nagane M, Nakada M, Suehiro S, Hata N, Kuroda J, Narita Y, Sonoda Y, Iwadate Y, Natsumeda M, Nakazato Y, Minami H, Hirata Y, Hagihara S, Nishikawa R.
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Journal Title
Int J Clin Oncol.
Volume: -
Issue: 12
Pages: 2205-2215
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[Journal Article] Impact of Inversion Time for FLAIR Acquisition on the T2-FLAIR Mismatch Detectability for IDH-Mutant, Non-CODEL Astrocytomas2021
Author(s)
Manabu Kinoshita, Hideyuki Arita, Masamichi Takahashi, Takehiro Uda, Junya Fukai, Kenichi Ishibashi, Noriyuki Kijima, Ryuichi Hirayama, Mio Sakai, Atsuko Arisawa, Hiroto Takahashi, Katsuyuki Nakanishi, Naoki Kagawa, Kouichi Ichimura, Yonehiro Kanemura, Yoshitaka Narita, Haruhiko Kishima
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Journal Title
Frontiers in Oncology
Volume: 10
Pages: 596448-596448
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[Journal Article] Efficacy of endovascular intratumoral embolization for meningioma: assessment using dynamic susceptibility contrast-enhanced perfusion-weighted imaging.2021
Author(s)
Asai K, Nakamura H, Watanabe Y, Nishida T, Sakai M, Arisawa A, Takagaki M, Arita H, Ozaki T, Kagawa N, Fujimoto Y, Nakanishi K, Kinoshita M, Kishima H.
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Journal Title
J Neurointerv Surg.
Volume: -
Issue: 12
Pages: 1167-1171
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Peer Reviewed
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[Journal Article] Activated leukocyte cell adhesion molecule expression correlates with the WNT subgroup in medulloblastoma and is involved in regulating tumor cell proliferation and invasion2020
Author(s)
Achiha T, Kijima N, Kodama Y, Kagawa N, Kinoshita M, Fujimoto Y, Nonaka M, Fukai J, Inoue A, Nishida N, Yamanaka T, Harada A, Mori K, Tsuyuguchi N, Uda T, Ishibashi K, Tomogane Y, Sakamoto D, Shofuda T, Yoshioka E, Kanematsu D, Mano M, Luu B, Taylor MD, Kanemura Y, Kishima H.
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Journal Title
PLoS One
Volume: 15
Issue: 12
Pages: e0243272-e0243272
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Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Diagnostic exposure to low-dose radiation and spontaneous regression in intracranial germ cell tumors2020
Author(s)
Naoki Kagawa, Ryuichi Hirayama, Shogo Fukuya, Chisato Yokota, Yasunori Fujimoto, Yasuyoshi Chiba, Daisuke Eino, Toru Umehara, Takanori Fukunaga, Manabu Kinoshita, and Haruhiko Kishima
Organizer
The 19th International Symposium on Pediatric Neuro-Oncology (ISPNO2020)
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[Presentation] Radiation-associated Intracranial Tumors In Childhood Cancer Survivors: Therapeutic Strategies And Its Problems2019
Author(s)
Naoki Kagawa, Chisato Yokota, Toru Umehara, Takamune Achiha, Takanori Fukunaga, Daisuke Eino, Shogo Fukuya, Yasuyoshi Chiba, Hideyuki Arita, Yasunori Fujimoto, Haruhiko Kishima.
Organizer
3rd Congress of Asian-Australasian Society for Pediatric Neurosurgery (AASPN2019)
Related Report
Int'l Joint Research
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