Identification of resistant clone for the chemotherapy of hepatocellular carcinoma using cell free DNA

2022 Fiscal Year Research-status Report

• Project/Area Number: 21K07950
• Research Institution: Kindai University
• Principal Investigator: 工藤 正俊 近畿大学, 医学部, 教授 (10298953)
• Co-Investigator(Kenkyū-buntansha): 西田 直生志 近畿大学, 医学部, 教授 (60281755)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 肝細胞癌 / 免疫チェックポイント阻害剤 / セルフリーDNA / 腫瘍微小免疫環境 / 無再発生存期間

Outline of Annual Research Achievements

肝細胞癌（肝癌）の治療後に免疫チェックポイント阻害剤(ICI)が投与された例を用い、再発予防と関連する免疫関連分子の解析を行った。32例に関し、免疫染色(IHC)にて評価した腫瘍免疫微小環境（TME）とICI投与下での再発の関連を解析した。免疫染色による腫瘍免疫環境(TME)の解析にはb-カテニン、GS、PD-1、PD-L1、CD8、とFoxp3を用い、腫瘍ゲノムの解析にはThermo FischerのTML assayにより、409の癌関連遺伝子変異、コピー数変化（CNV）、tumor mutation load (TML)を解析した。またRosheのCAPP-Seqにより血漿からctDNA検出を検出し、mlあたりvariant alleleが10コピー以上検出された場合をMRD陽性と判定した。
b-カテニンとGSの染色結果より肝癌をb-catenin経路活性化群、非活性化群、TME状態により4群（hot型、exhausted型、cold型、Treg型）に分類した。ICI投与による術後無再発生存期間(RFS)はb-カテニン経路非活性化群で活性化群より有意に長く(p=0.0191)、またhot/exhausted型はcold/Treg型に比較して有意に長かった(p＜0.0001)。次に肝癌コホートでb-カテニン活性化に関わるCNVに注目した。b-カテニンにより活性化される転写因子TCF3, 4、およびMYCのlocusにCNVのある例はない例と比べて再発例が多く、PD-1抗体投与下での根治術後のRFSが有意に短いという結果が得られた。腫瘍組織のTMBとPD-1投与下での再発に関しては、再発例と無再発例でTMB量に差がなく、またRFSにも差がなかった。MRDに関しては、この症例数では有意差はないものの、根治術後にMRD陽性例ではRFSが短い傾向にあった。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

本研究計画では、肝癌根治術後のアジュバント療法としての免疫チェックポイント阻害剤を使用中に腫瘍が再発した例での遺伝子変異の特徴、チロシンキナーゼ阻害剤による腫瘍反応後に再増悪を来した例の遺伝子変異の特徴を、血中circulating tumor DNA（ctDNA）を用いて解析することを目的としている。今回は前年度の成果から、さらに癌関連遺伝子変異、コピー数変化（CNV）、tumor mutation load (TML)をより詳細に解析した。今回の肝癌コホートではβカテニン遺伝子の変異例が1例、APC変異例が2例しかなかったため、βカテニン経路活性化変異に加え、βカテニンにより活性化される転写因子TCF3, 4、およびMYCのcopy number gain (CNG)に注目した。興味深いことに、これらのlocusにCNVのある例はない例と比べて再発例が多く、PD-1抗体投与下での根治術後のRFSが有意に短いという結果が得られた。また、症例背景に関して血中AFP値との関連を見たところ、術後でもAFPが8ng/ml以上の例では全例MRD陽性であり、血中AFP値が5未満の例でも約半数がMRD陽性となっていた。すなわち、肝癌術後に腫瘍マーカーが低下しても、約半数残存腫瘍がある可能性が示唆された。上記の成果より、本研究は概ね順調の進展していると言える。

Strategy for Future Research Activity

今後は、より長期間のフォローによりイベント数が増えてから再解析する予定である。また、研究計画に基づき、チロシンキナーゼ阻害剤（TKI）における耐性変異クローンを同定する目的で、TKI投与により、腫瘍縮小が得られた症例中、治療前に手術あるいは腫瘍生検によるパラフィン包埋組織が利用可能な例を対象として、治療前の腫瘍組織の遺伝子異常をOncomine Tumor Mutation Load Assayにて、治療開始後、及び腫瘍の再増悪時のcfDNA の遺伝子変異をAVENIO ctDNA Surveillance panel にて解析する。

Causes of Carryover

ほぼ予定通りの支出である。標本作成数に変更があり、若干の次年度使用額が生じたが、次年度の標本作成に使用する予定である。

Research Products

• [Journal Article] Impact of body mass index in patients receiving atezolizumab plus bevacizumab for hepatocellular carcinoma (2023)
  • Author(s): Vithayathil M, D'Alessio A, Fulgenzi CAM, Nishida N, Schonlein M, von Felden J, Schulze K, Wege H, Saeed A, Wietharn B, Hildebrand H, Wu L, Ang C, Marron TU, Weinmann A, Galle PR, Bettinger D, Bengsch B, Vogel A, Balcar L, Kudo M et al., et al.
  • Journal Title: Hepatology International Volume: ー Pages: ー
  • DOI: 10.1007/s12072-023-10491-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Advances in Immunotherapy for Hepatocellular Carcinoma (2023)
  • Author(s): Hagiwara S, Nishida N, Kudo M.
  • Journal Title: Cancers Volume: 15 (7) Pages: 2070
  • DOI: 10.3390/cancers15072070
  • Peer Reviewed / Open Access
• [Journal Article] Survival outcomes from atezolizumab plus bevacizumab versus Lenvatinib in Child Pugh B unresectable hepatocellular carcinoma patients (2023)
  • Author(s): Rimini M, Persano M, Tada T, Suda G, Shimose S, Kudo M, Cheon J, Finkelmeier F, Lim HY, Presa J, Salani F, Lonardi S, Piscaglia F, Kumada T, Sakamoto N, Iwamoto H, Aoki T, Chon HJ, Himmelsbach V, Schirripa M, Montes M, Vivaldi C, Solda C, Hiraoka A, Sho T, Niizeki T, Nishida N, et al.
  • Journal Title: Journal of Cancer Research and Clinical Oncology Volume: ー Pages: ー
  • DOI: 10.1007/s00432-023-04678-2
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Real-World Data for Atezolizumab Plus Bevacizumab in Unresectable Hepatocellular Carcinoma: How Does Adherence to the IMbrave150 Trial Inclusion Criteria Impact Prognosis? (2023)
  • Author(s): Rimini M, Persano M, Tada T, Suda G, Shimose S, Kudo M, Cheon J, Finkelmeier F, Lim HY, Presa J, Masi G, Yoo C, Lonardi S, Piscaglia F, Kumada T, Sakamoto N, Iwamoto H, Aoki T, Chon HJ, Himmelsbach V, Pressiani T, Montes M, Vivaldi C, Solda C, Hiraoka A, Sho T, Niizeki T, Nishida N, et al.
  • Journal Title: Targeted Oncology Volume: 18 Pages: 221～233
  • DOI: 10.1007/s11523-023-00953-x
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Role of the prognostic nutritional index in predicting survival in advanced hepatocellular carcinoma treated with atezolizumab plus bevacizumab (2023)
  • Author(s): Persano M, Rimini M, Tada T, Suda G, Shimose S, Kudo M, Cheon J, Finkelmeier F, Lim HY, Presa Ramos J, Masi G, Yoo C, Lonardi S, Stefanini B, Kumada T, Sakamoto N, Iwamoto H, Aoki T, Chon HJ, Himmelsbach V, Montes M, Vivaldi C, Solda C, Hiraoka A, Sho T, Niizeki T, Nishida N, et al.
  • Journal Title: Oncology Volume: ー Pages: ー
  • DOI: 10.1159/000528818
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Outcomes of beta blocker use in advanced hepatocellular carcinoma treated with immune checkpoint inhibitors (2023)
  • Author(s): Wu YL, van Hyfte G, Ozbek U, Reincke M, Gampa A, Mohamed YI, Nishida N, Wietharn B, Amara S, Lee PC, Scheiner B, Balcar L, Pinter M, Vogel A, Weinmann A, Saeed A, Pillai A, Rimassa L, Naqash AR, Muzaffar M, Huang YH, Kaseb AO, Kudo M, Pinato DJ, Ang C.
  • Journal Title: Frontiers in Oncology Volume: 13 Pages: 128569～1128569
  • DOI: 10.3389/fonc.2023.1128569
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Artificial intelligence models for the diagnosis and management of liver diseases (2023)
  • Author(s): Nishida N, Kudo, M
  • Journal Title: Ultrasonography Volume: 42 (1) Pages: 10～19
  • DOI: 10.14366/usg.22110
  • Peer Reviewed
• [Journal Article] Progression patterns and therapeutic sequencing following immune checkpoint inhibition for hepatocellular carcinoma: An international observational study (2023)
  • Author(s): Talbot T, D'Alessio A, Pinter M, Balcar L, Scheiner B, Marron TU, Jun T, Dharmapuri S, Ang C, Saeed A, Hildebrand H, Muzaffar M, Fulgenzi CAM, Amara S, Naqash AR, Gampa A, Pillai A, Wang Y, Khan U, Lee PC, Huang YH, Bengsch B, Bettinger D, Mohamed YI, Kaseb A, Pressiani T, Nishida N, Kudo M, et al.
  • Journal Title: Liver International Volume: 43 (3) Pages: 695～707
  • DOI: 10.1111/liv.15502
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Atezolizumab plus bevacizumab versus lenvatinib for unresectable hepatocellular carcinoma: a large real-life worldwide population (2023)
  • Author(s): Casadei-Gardini A, Rimini M, Tada T, Suda G, Shimose S, Kudo M, Cheon J, Finkelmeier F, Lim HY, Rimassa L, Presa J, Masi G, Yoo C, Lonardi S, Tovoli F, Kumada T, Sakamoto N, Iwamoto H, Aoki T, Chon HJ, Himmelsbach V, Pressiani T, Montes M, Vivaldi C, Solda C, Piscaglia F, Hiraoka A, Nishida N, et al.
  • Journal Title: European Journal of Cancer Volume: 180 Pages: 9～20
  • DOI: 10.1016/j.ejca.2022.11.017
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Successful initial tofacitinib treatment for acute severe ulcerative colitis with steroid resistance: a case series (2022)
  • Author(s): Komeda Y, Kono M, Kashida H, Tribonias G, Masaki S, Takada R, Nagai T, Hagiwara S, Nishida N, Takenaka M, Honjo H, Matsui S, Tsuji N, Kudo M.
  • Journal Title: Annals of Gastroenterology Volume: 35 (1) Pages: 97～102
  • DOI: 10.20524/aog.2022.0768
  • Peer Reviewed
• [Journal Article] Clinical outcomes with atezolizumab plus bevacizumab or lenvatinib in patients with hepatocellular carcinoma: a multicenter real-world study (2022)
  • Author(s): Persano M, Rimini M, Tada T, Suda G, Shimose S, Kudo M, Cheon J, Finkelmeier F, Lim HY, Rimassa L, Presa J, Masi G, Yoo C, Lonardi S, Tovoli F, Kumada T, Sakamoto N, Iwamoto H, Aoki T, Chon HJ, Himmelsbach V, Pressiani T, Kawaguchi T, Montes M, Vivaldi C, Solda C, Piscaglia F, Hiraoka A, Sho T, Nishida N, et al.
  • Journal Title: Journal of Cancer Research and Clinical Oncology Volume: ー Pages: ー
  • DOI: 10.1007/s00432-022-04512-1
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios as Prognostic Biomarkers in Unresectable Hepatocellular Carcinoma Treated with Atezolizumab plus Bevacizumab (2022)
  • Author(s): Wu YL, Fulgenzi CAM, D'Alessio A, Cheon J, Nishida N, Saeed A, Wietharn B, Cammarota A, Pressiani T, Personeni N, Pinter M, Scheiner B, Balcar L, Huang YH, Phen S, Naqash AR, Vivaldi C, Salani F, Masi G, Bettinger D, Vogel A, Schonlein M, von Felden J, Schulze K, Wege H, Galle PR, Kudo M, et al
  • Journal Title: Cancers Volume: 14 (23) Pages: 5834
  • DOI: 10.3390/cancers14235834
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Reproducible safety and efficacy of atezolizumab plus bevacizumab for HCC in clinical practice: Results of the AB-real study (2022)
  • Author(s): Fulgenzi CAM, Cheon J, D'Alessio A, Nishida N, Ang C, Marron TU, Wu L, Saeed A, Wietharn B, Cammarota A, Pressiani T, Personeni N, Pinter M, Scheiner B, Balcar L, Napolitano A, Huang YH, Phen S, Naqash AR, Vivaldi C, Salani F, Masi G, Bettinger D, Vogel A, Schonlein M, von Felden J, Schulze K, Kudo M, et al.
  • Journal Title: European Journal of Cancer Volume: 175 Pages: 204～213
  • DOI: 10.1016/j.ejca.2022.08.024
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Impact of older age in patients receiving atezolizumab and bevacizumab for hepatocellular carcinoma (2022)
  • Author(s): Vithayathil M, D'Alessio A, Fulgenzi CAM, Nishida N, Schonlein M, von Felden J, Schulze K, Wege H, Saeed A, Wietharn B, Hildebrand H, Wu L, Ang C, Marron TU, Weinmann A, Galle PR, Bettinger D, Bengsch B, Vogel A, Balcar L, Scheiner B, Lee PC, Huang YH, Amara S, Muzaffar M, Naqash AR, Cammarota A, Kudo M, et al.
  • Journal Title: Liver International Volume: 42 (11) Pages: 2538～2547
  • DOI: 10.1111/liv.15405
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Prognostic Factors for Overall Survival in Patients with HCV-Related HCC Undergoing Molecular Targeted Therapies: Beyond a Sustained Virological Response (2022)
  • Author(s): Minami Y, Aoki T, Chishina H, Takita M, Hagiwara S, Ida H, Ueshima K, Nishida N, Kudo M.
  • Journal Title: Cancers Volume: 14 (19) Pages: 4850
  • DOI: 10.3390/cancers14194850
  • Peer Reviewed / Open Access
• [Journal Article] Progression from early to advanced stage of immune‐related cholangitis (2022)
  • Author(s): Hagiwara S, Yoshida T, Nishida N, Ida H, Ueshima K, Minami Y, Takita M, Aoki T, Morita M, Cishina H, Komeda Y, Yoshida A, Hayashi H, Nakagawa K, Kudo M.
  • Journal Title: Hepatology Research Volume: 52 (10) Pages: 888～892
  • DOI: 10.1111/hepr.13817
  • Peer Reviewed
• [Journal Article] Preliminary evidence of safety and tolerability of atezolizumab plus bevacizumab in patients with hepatocellular carcinoma and Child‐Pugh A and B cirrhosis: A real‐world study (2022)
  • Author(s): Gaillard VE, Saeed A, Wietharn B, Hildebrand H, Wu L, Ang C, Marron TU, Weinmann A, Galle PR, Bettinger D, Bengsch B, Vogel A, Balcar L, Scheiner B, Lee PC, Huang YH, Amara S, Muzaffar M, Naqash AR, Cammarota A, Personeni N, Pressiani T, Sharma R, Pinter M, Cortellini A, Kudo M, et al.
  • Journal Title: Hepatology Volume: 76 (4) Pages: 1000～1012
  • DOI: 10.1002/hep.32468
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinical implication of immune checkpoint inhibitor on the chronic hepatitis B virus infection (2022)
  • Author(s): Hagiwara S, Nishida N, Ida H, Ueshima K, Minami Y, Takita M, Aoki T, Morita M, Chishina H, Komeda Y, Yoshida A, Hayashi H, Nakagawa K, Kudo M.
  • Journal Title: Hepatology Research Volume: 52 (9) Pages: 754～761
  • DOI: 10.1111/hepr.13798
  • Peer Reviewed
• [Journal Article] Validation of the easy‐to‐use lenvatinib prognostic index to predict prognosis in advanced hepatocellular carcinoma patients treated with lenvatinib (2022)
  • Author(s): Rimini M, Kang W, Burgio V, Persano M, Aoki T, Shimose S, Tada T, Kumada T, Sho T, Lai E, Celsa C, Campani C, Tonnini M, Tamburini E, Hiraoka A, Takaguchi K, Nishida N, Iwamoto H, Itobayashi E, Tsuji K, Sakamoto N, Ishikawa T, Toyoda H, Kudo M, et al.
  • Journal Title: Hepatology Research Volume: 52 (12) Pages: 1050～1059
  • DOI: 10.1111/hepr.13824
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Patterns and outcomes of subsequent therapy after immune checkpoint inhibitor discontinuation in HCC (2022)
  • Author(s): Sharma R, Pillai A, Marron TU, Fessas P, Saeed A, Jun T, Dharmapuri S, Szafron D, Naqash AR, Gampa A, Wang Y, Khan U, Muzaffar M, Lee CJ, Lee PC, Bulumulle A, Paul S, Bettinger D, Hildebrand H, Yehia M, Pressiani T, Kaseb A, Huang YH, Ang C, Kudo M, Nishida N, Personeni N, Rimassa L, Pinato DJ.
  • Journal Title: Hepatology Communications Volume: 6 (7) Pages: 1776～1785
  • DOI: 10.1002/hep4.1927
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Integrated use of PD-1 inhibition and transarterial chemoembolization for hepatocellular carcinoma: evaluation of safety and efficacy in a retrospective, propensity score-matched study (2022)
  • Author(s): Marinelli B, Kim E, D'Alessio A, Cedillo M, Sinha I, Debnath N, Kudo M, Nishida N, Saeed A, Hildebrand H, Kaseb AO, Abugabal YI, Pillai A, Huang YH, Khan U, Muzaffar M, Naqash AR, Patel R, Fischman A, Bishay V, Bettinger D, Sung M, Ang C, Schwartz M, Pinato DJ, Marron T.
  • Journal Title: Journal for Immunotherapy of Cancer Volume: 10(6) Pages: e004205
  • DOI: 10.1136/jitc-2021-004205
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Value of artificial intelligence with novel tumor tracking technology in the diagnosis of gastric submucosal tumors by contrast‐enhanced harmonic endoscopic ultrasonography (2022)
  • Author(s): Tanaka H, Kamata K, Ishihara R, Handa H, Otsuka Y, Yoshida A, Yoshikawa T, Ishikawa R, Okamoto A, Yamazaki T, Nakai A, Omoto S, Minaga K, Yamao K, Takenaka M, Watanabe T, Nishida N, Kudo M.
  • Journal Title: Journal of Gastroenterology and Hepatology Volume: 37 (5) Pages: 841～846
  • DOI: 10.1111/jgh.15780
  • Peer Reviewed
• [Journal Article] Role of phlebotomy in the treatment of liver damage related to erythropoietic porphyria (2022)
  • Author(s): Hagiwara S, Nishida N, Ida H, Ueshima K, Minami Y, Takita M, Aoki T, Morita M, Chishina H, Komeda Y, Yoshida A, Park AM, Sato M, Kawada A, Nakano H, Nakagawa H, Kudo M.
  • Journal Title: Scientific Reports Volume: 12 (1) Pages: 6100-6100
  • DOI: 10.1038/s41598-022-10089-z
  • Peer Reviewed / Open Access
• [Journal Article] Artificial intelligence (AI) models for the ultrasonographic diagnosis of liver tumors and comparison of diagnostic accuracies between AI and human experts. (2022)
  • Author(s): Nishida Naoshi、Yamakawa Makoto、Shiina Tsuyoshi、Mekada Yoshito、Nishida Mutsumi、Sakamoto Naoya、Nishimura Takashi、Iijima Hiroko、Hirai Toshiko、Takahashi Ken、Sato Masaya、Tateishi Ryosuke、Ogawa Masahiro、Mori Hideaki、Kitano Masayuki、Toyoda Hidenori、Ogawa Chikara、Kudo Masatoshi、JSUM A. I. investigators
  • Journal Title: Journal of Gastroenterology Volume: 57 Pages: 309～321
  • DOI: 10.1007/s00535-022-01849-9
  • Peer Reviewed / Open Access
• [Presentation] 腹部超音波動画からの肝腫瘍検出AIプログラムの開発 (2022)
  • Author(s): 目加田 慶人, 西田直 生志, 工藤 正俊
  • Organizer: JDDW2022 統合プログラム6: AI研究の実装化に向けた課題
• [Presentation] 肝細胞癌の微小環境と再発予防における免疫チェックポイント阻害剤の効果 (2022)
  • Author(s): 西田 直生志, 上嶋 一臣, 工藤 正俊
  • Organizer: JDDW2022 統合プログラム5 消化肝癌における免疫療法の実際
• [Presentation] 切除不能肝細胞癌におけるhyper progressive diseaseの頻度と有効な後治療 (2022)
  • Author(s): 青木 智子, 西田 直生志, 工藤 正俊
  • Organizer: JDDW2022 ワークショップ8 進行肝癌薬物療法の課題と展望
• [Presentation] Selection of Anti-PD-1 Antibody Effective Group Using Tumor Immunological Microenvironment (2022)
  • Author(s): Masahiro Morita, Naoshi Nishida, Masatoshi Kudo
  • Organizer: The Asian Pacific Association for the Study of the Liver [APASL] 2022, Workshop 15
  • Int'l Joint Research / Invited
• [Presentation] Examination of NASH -related Liver Carcinogenesis from Non -developed Fibrosis (2022)
  • Author(s): Satoru Hagiwara, Naoshi Nishida, Masatoshi Kudo
  • Organizer: The Asian Pacific Association for the Study of the Liver [APASL] Oncology 2022, Workshop 9
  • Int'l Joint Research / Invited
• [Presentation] 免疫チェックポイント阻害剤投与に伴うirAE肝障害、HBV再活性化についての検討 (2022)
  • Author(s): 萩原 智, 西田 直生志, 工藤 正俊
  • Organizer: 第58回日本肝臓学会総会 パネルディスカッション6: 治療起因性肝障害のマネジメント-DILI・HBV再活性化・irAE・IRIS
• [Presentation] Phase 2根治後NIVOLVE試験における奏功症例と特徴 (2022)
  • Author(s): 青木 智子, 西田 直生志, 工藤 正俊
  • Organizer: 第58回肝臓学会総会 シンポジウム2: 肝がんのマネジメント-発がん予防・内科治療・外科治療・再発予防
• [Presentation] 人工知能(AI)によるB-mode超音波検査の 肝腫瘍鑑別支援と肝癌診療への展開 (2022)
  • Author(s): 西田直生志, 工藤正俊
  • Organizer: 第58回肝癌研究会 シンポジウム5: ビッグデータやAI、IoT による新たな肝癌診療モデルの構築
• [Presentation] 複合免疫療法時代におけるイメージングバイオマーカーとしてのEOB-MRIの役割 (2022)
  • Author(s): 青木智子, 西田直生志, 上嶋一臣, 盛田真弘, 千品寛和, 田北雅弘, 南康範, 依田広, 祖父江慶太郎, 鶴崎正勝, 工藤正俊
  • Organizer: 第58回日本肝癌研究会; パネルディスカッション8 肝癌におけるPrecision Oncology
• [Presentation] 複合免疫療法時代におけるhyper progressive disease (HPD) (2022)
  • Author(s): 青木智子, 西田直生志, 上嶋一臣, 盛田真弘, 千品寛和, 田北雅弘, 南康範, 萩原智, 依田広, 鶴崎正勝, 工藤正俊
  • Organizer: 第58回日本肝癌研究会 パネルディスカッション5; 肝癌免疫療法の治療向上を目指して
• [Presentation] 肝疾患の遺伝子異常による病態解明と臨床展開 (2022)
  • Author(s): 萩原智, 西田直生志, 工藤正俊
  • Organizer: 第108回日本消化器病学会総会 ワークショップ10 肝疾患の遺伝子解析による病態解明と臨床展開
• [Presentation] 肝細胞癌における腫瘍微小免疫環境と免疫チェックポイント阻害剤の効果 (2022)
  • Author(s): 西田 直生志, 上嶋 一臣, 工藤 正俊
  • Organizer: 第108回日本消化器病学会総会 シンポジウム5 消化器癌における免疫治療と分子標的治療の基礎研究と臨床