2026/03/10 更新

写真a

クリバヤシ　タダヒロ
栗林　忠弘
Kuribayashi Tadahiro
所属
医歯薬学域 助教（特任）
職名
助教（特任）
外部リンク
 

論文

  • Clinical Characteristics and Spatial Transcriptome Analysis of Non-Small Cell Lung Cancers Exhibiting Early Alectinib Resistance: A Retrospective OLCSG Study. 査読 国際誌

    Tadahiro Kuribayashi, Go Makimoto, Kadoaki Ohashi, Shuta Tomida, Hirofumi Inoue, Toshihide Yokoyama, Shoichi Kuyama, Yuka Kato, Kenichiro Kudo, Naokatsu Horita, Hiroe Kayatani, Masaaki Inoue, Keisuke Sugimoto, Kiichiro Ninomiya, Yoshinobu Maeda, Yosuke Togashi, Katsuyuki Hotta

    Cancer research communications   6 ( 2 )   284 - 293   2026年2月

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    担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

    UNLABELLED: Some anaplastic lymphoma kinase (ALK) gene rearrangement-positive lung cancers show early resistance, within 3 months, to alectinib. This study investigated the clinical and molecular characteristics of these patients. We analyzed patients with unresectable stage III/IV disease without indications for radical radiotherapy and recurrent ALK-positive lung cancer who received alectinib as the primary ALK tyrosine kinase inhibitor between 2013 and 2021 at nine hospitals. In total, 103 patients were included. The median age was 65 years; 44 were male and 22 had brain metastases. The median progression-free survival and overall survival (OS) were 28.7 and 80.6 months. Nineteen patients treated for ≤3 months and 84 treated for >3 months were categorized into the early resistance and responder groups, respectively. The early resistance group had significantly shorter OS (8.4 months vs. not estimable, P < 0.001) and was significantly more likely to have brain metastases (42% vs. 17%, P = 0.027). They also showed elevated inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR). Univariate analysis identified brain metastases and high NLR as significant predictors of early resistance. Spatial transcriptome analysis and immunohistochemical staining revealed upregulation of annexin A1 (ANXA1), a calcium-dependent phospholipid-binding protein involved in inflammation and cancer progression, in the early resistance group. Interleukin 6 stimulation, prompted by elevated inflammatory markers, increased ANXA1 expression and reduced alectinib sensitivity. Knockdown of ANXA1 improved alectinib sensitivity in alectinib-resistant cells. In conclusion, brain metastases and high NLR are associated with early resistance. ANXA1 may play an important role in mediating early resistance. New treatment options for the early resistance group are required. SIGNIFICANCE: Some ALK-positive lung cancers show early resistance to alectinib. This study found brain metastases and elevated NLR associated with early resistance. Spatial transcriptomics and functional analysis suggested involvement of ANXA1. These results reveal clinical and molecular biomarkers that may guide treatment strategies for early resistance to alectinib.

    DOI： 10.1158/2767-9764.CRC-25-0545

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  • Colony-Stimulating Factor-1 Receptor Inhibitor Augments Osimertinib-Induced Antitumor Immunity via Suppression of Macrophages in Lung Cancer Harboring EGFR Mutation. 査読 国際誌

    Sachi Okawa, Shuta Tomida, Tadahiro Kuribayashi, Jun Nishimura, Takamasa Nakasuka, Atsuko Hirabae, Naofumi Hara, Hirofumi Inoue, Go Makimoto, Kiichiro Ninomiya, Kammei Rai, Eiki Ichihara, Katuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura, Kadoaki Ohashi

    Molecular cancer therapeutics   24 ( 11 )   1763 - 1774   2025年11月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    Persister cancer cells, which reversibly adapt to survive epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) treatment, contribute to the incurability of EGFR-mutant lung cancer. We previously reported that gefitinib induces CD8⁺ T cell-related tumor immunity in a genetically engineered mouse model (GEMM). This study investigates the tolerance of persister cancer cells to EGFR-TKI-induced tumor immunity in this model. Egfr-mutated lung cancer cells (C57BL/6/EgfrdelE748-A752) from GEMM were transplanted subcutaneously into wild-type C57BL/6J mice. Persistent tissues under osimertinib treatment were analyzed using digital spatial transcriptional profiling (DSP), immunohistochemical staining (IHC), and flow cytometry (FCM). The anti-tumor effect of osimertinib peaked at 14 days, leaving a small population of persister cancer cells. The number of PD-1⁺ CD8⁺ cells increased in the tumor microenvironment (TME), and CD8⁺ cell depletion attenuated the anti-tumor effect of osimertinib. DSP revealed upregulated expression of M2 macrophage-related genes in the TME of persister cancer cells. Consistently, IHC and FCM confirmed an increased number of CD206⁺ macrophages in the TME. Combining osimertinib with the colony-stimulating factor-1 receptor (CSF1R) inhibitor pexidartinib reduced CD206⁺ macrophages and enhanced the efficacy of osimertinib. Elevated granzyme or CD107 expression on CD8⁺ cells in the TME suggests that macrophages negatively affect osimertinib-induced anti-tumor immunity. M2-like macrophages may contribute to immune tolerance of persister cancer cells against EGFR-TKI-induced tumor immunity. A clinical trial evaluating combined osimertinib and CSF1R inhibitor therapy is warranted for Egfr-mutated lung cancer.

    DOI： 10.1158/1535-7163.MCT-25-0002

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  • Plasma S100A8/A9 level predicts response to immune checkpoint inhibitors in patients with advanced non-small cell lung cancer. 査読 国際誌

    Tadahiro Kuribayashi, Rie Kinoshita, Kiichiro Ninomiya, Go Makimoto, Toshio Kubo, Kammei Rai, Eiki Ichihara, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura, Shinichi Toyooka, Masakiyo Sakaguchi, Kadoaki Ohashi

    Scientific reports   15 ( 1 )   2577 - 2577   2025年1月

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    担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

    Blood-based predictive markers for the efficacy of immune checkpoint inhibitors (ICIs) have not yet been established. We investigated the association of the plasma level of S100A8/A9 with the efficacy of immunotherapy. We evaluated patients with unresectable stage III/IV or recurrent non-small cell lung cancer (NSCLC) who were treated with ICIs at Okayama University Hospital. The pre-treatment plasma levels of S100A8/A9 were analyzed. Eighty-one eligible patients were included (median age, 69 years). Sixty-two patients were men, 54 had adenocarcinoma, 74 had performance status (PS) 0-1, and 47 received ICIs as first-line treatment. The median time to treatment failure (TTF) for ICIs was 5.7 months, and the median overall survival (OS) was 19.6 months. The TTF and OS were worse in patients with high plasma S100A8/A9 levels (≥ 2.475 µg/mL) (median TTF: 4.3 vs. 8.5 months, p = 0.009; median OS: 15.4 vs. 38.0 months, p = 0.001). Multivariate analysis revealed that PS ≥ 2, liver metastasis, and high plasma S100A8/A9 levels were significantly associated with short TTF and OS. In conclusion, plasma S100A8/A9 level may have a limited effect on ICI therapy for NSCLC.

    DOI： 10.1038/s41598-025-87232-z

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  • Concomitant osimertinib and antituberculosis therapy in an elderly patient with EGFR-mutated lung cancer and pulmonary tuberculosis: A case report. 査読 国際誌

    Hiroaki Matsuura, Hisao Higo, Tadahiro Kuribayashi, Akihiko Tamaoki, Takamasa Nakasuka, Mari Uno, Go Makimoto, Kiichiro Ninomiya, Masanori Fujii, Kammei Rai, Eiki Ichihara, Katsuyuki Hotta, Nobuaki Miyahara, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura, Kadoaki Ohashi

    Thoracic cancer   15 ( 17 )   1390 - 1394   2024年6月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    The concurrent incidence of lung cancer and tuberculosis is expected to escalate due to the projected growth in the older population. Combination therapy with osimertinib and antituberculosis drugs has not been well-established. We report a case of successful treatment involving the concomitant administration of osimertinib and antituberculosis drugs in an older patient, an 89-year-old female, diagnosed with epidermal growth factor receptor (EGFR)-mutant lung cancer and pulmonary tuberculosis. Accumulating evidence is warranted to develop an optimal treatment strategy for patients with lung cancer and tuberculosis.

    DOI： 10.1111/1759-7714.15324

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  • 非小細胞肺癌 分子標的治療 ALK融合遺伝子変異陽性非小細胞肺癌におけるアレクチニブ早期耐性患者の臨床的特徴を明らかにするための後ろ向きコホート研究

    横山 俊秀, 栗林 忠弘, 槇本 剛, 久山 彰一, 加藤 有加, 工藤 健一郎, 堀田 尚克, 萱谷 紘枝, 井上 政昭, 杉本 啓介, 大橋 圭明, 堀田 勝幸

    日本呼吸器学会誌   13 ( 増刊 )   190 - 190   2024年3月

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    記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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  • Clinical characteristics of patients treated with immune checkpoint inhibitors in EGFR-mutant non-small cell lung cancer: CS-Lung-003 prospective observational registry study. 査読 国際誌

    Tadahiro Kuribayashi, Kadoaki Ohashi, Kazuya Nishii, Kiichiro Ninomiya, Yukari Tsubata, Nobuhisa Ishikawa, Masahiro Kodani, Nobuhiro Kanaji, Masahiro Yamasaki, Kazunori Fujitaka, Shoichi Kuyama, Nagio Takigawa, Nobukazu Fujimoto, Tetsuya Kubota, Masaaki Inoue, Keiichi Fujiwara, Shingo Harita, Ichiro Takata, Kenji Takada, Sachi Okawa, Katsuyuki Kiura, Katsuyuki Hotta

    Journal of cancer research and clinical oncology   150 ( 2 )   89 - 89   2024年2月

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    担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

    PURPOSE: Immune checkpoint inhibitors (ICIs) are ineffective against epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). This study aimed to investigate the clinical characteristics of patients who were treated or not treated with ICIs, and of those who benefit from immunotherapy in EGFR-mutant NSCLC. METHODS: We analyzed patients with unresectable stage III/IV or recurrent NSCLC harboring EGFR mutations using a prospective umbrella-type lung cancer registry (CS-Lung-003). RESULTS: A total of 303 patients who met the eligibility criteria were analyzed. The median age was 69 years; 116 patients were male, 289 had adenocarcinoma, 273 had major mutations, and 67 were treated with ICIs. The duration of EGFR-TKI treatment was longer in the Non-ICI group than in the ICI group (17.1 vs. 12.7 months, p < 0.001). Patients who received ICIs for more than 6 months were categorized into the durable clinical benefit (DCB) group (24 patients), and those who received ICIs for less than 6 months into the Non-DCB group (43 patients). The overall survival in the DCB group exhibited longer than the Non-DCB group (69.3 vs. 47.1 months), and an equivalent compared to that in the Non-ICI group (69.3 vs. 68.9 months). Multivariate analysis for time to next treatment (TTNT) of ICIs showed that a poor PS was associated with a shorter TTNT [hazard ratio (HR) 3.309; p < 0.001]. Patients who were treated with ICIs and chemotherapy combination were associated with a longer TTNT (HR 0.389; p = 0.003). In addition, minor EGFR mutation was associated with a long TTNT (HR 0.450; p = 0.046). CONCLUSION: ICIs were administered to only 22% of patients with EGFR-mutated lung cancer, and they had shorter TTNT of EGFR-TKI compared to other patients. ICI treatment should be avoided in EGFR mutated lung cancer with poor PS but can be considered for lung cancer with EGFR minor mutations. Pathological biomarker to predict long-term responders to ICI are needed.

    DOI： 10.1007/s00432-024-05618-4

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  • Fulminant Myocarditis for Non-small-cell Carcinoma of the Lung with Nivolumab and Ipilimumab Plus Chemotherapy. 査読

    Tomoka Nishimura, Kiichiro Ninomiya, Mitsutaka Nakashima, Satoshi Akagi, Tadahiro Kuribayashi, Hisao Higo, Katsuyuki Hotta, Yoshinobu Maeda, Hiroshi Ito, Katsuyuki Kiura

    Internal medicine (Tokyo, Japan)   62 ( 9 )   1319 - 1322   2023年5月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    A 59-year-old man with a high level of antinuclear antibody received nivolumab and ipilimumab plus chemotherapy for lung cancer. Two weeks after the second course, he was admitted with a fever and severe fatigue. Laboratory studies showed elevated markers of myocardial damage, and a myocardial biopsy showed inflammatory cell infiltration, damaged myocardial fibers. Myocarditis was diagnosed as an immune-related adverse event (irAE), and high-dose corticosteroids were initiated. However, his cardiac function rapidly worsened, and he died on the fifth day after admission. There is no established treatment strategy for fulminant myocarditis as an irAE, and the further exploration of viable treatment strategies is required.

    DOI： 10.2169/internalmedicine.0505-22

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  • Reply to "Benralizumab as a First-line Treatment for ABPA: Is It Really Indicated?". 査読

    Hiroaki Matsuura, Keiichi Fujiwara, Hiroki Omori, Kiriko Onishi, Tadahiro Kuribayashi, Sho Mitsumune, Yuki Takigawa, Kenichiro Kudo, Akiko Sato, Ken Sato, Takuo Shibayama

    Internal medicine (Tokyo, Japan)   60 ( 15 )   2521 - 2521   2021年8月

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  • Successful Treatment with Benralizumab for Allergic Bronchopulmonary Aspergillosis That Developed after Disastrous Heavy Rainfall in Western Japan. 査読

    Hiroaki Matsuura, Keiichi Fujiwara, Hiroki Omori, Kiriko Onishi, Tadahiro Kuribayashi, Sho Mitsumune, Yuki Takigawa, Kenichiro Kudo, Daisuke Minami, Akiko Sato, Ken Sato, Takuo Shibayama

    Internal medicine (Tokyo, Japan)   60 ( 9 )   1443 - 1450   2021年5月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    We herein report a 56-year-old woman who developed allergic bronchopulmonary aspergillosis (ABPA) possibly due to fungal exposure after disastrous heavy rainfall in Western Japan in 2018. She was diagnosed with ABPA complicated with asthma, increased peripheral blood eosinophil count, elevation of specific immunoglobulin E for Aspergillus fumigatus, positive Aspergillus fumigatus precipitation antibody reaction test results, and notable chest computed tomography findings. After treatment with benralizumab, her symptoms, peripheral blood eosinophil count, radiological findings, and respiratory function dramatically improved. The administration of benralizumab appears to be an effective treatment strategy for ABPA.

    DOI： 10.2169/internalmedicine.6217-20

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  • Thrombotic Microangiopathy Associated with Gemcitabine in Non-Small Cell Lung Cancer: A Case Report. 査読 国際誌

    Tadahiro Kuribayashi, Keiichi Fujiwara, Kiriko Onishi, Sho Mitsumune, Yuki Takigawa, Hiromi Watanabe, Kenichiro Kudo, Akiko Sato, Ken Sato, Masashi Kitagawa, Kosuke Ota, Yoko Shinno, Takuo Shibayama

    Case reports in oncology   14 ( 3 )   1712 - 1718   2021年

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    担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

    A 69-year-old man with refractory lung adenocarcinoma was treated with gemcitabine and vinorelbine. Dyspnea and hypertension developed after the 17th cycle of chemotherapy. Laboratory findings revealed intravascular hemolysis and renal dysfunction. Thrombotic microangiopathy (TMA) was confirmed by renal biopsy. Antihypertensive and steroid therapies were ineffective. After plasmapheresis, intravascular hemolysis and renal dysfunction gradually improved. However, the disease progressed, and he died 6 months after TMA diagnosis. Autopsy revealed similar pathological findings to those of the renal biopsy. It is important to discontinue gemcitabine at the onset of TMA and consider TMA when using gemcitabine for long periods.

    DOI： 10.1159/000520484

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  • Optic Perineuritis Associated with Nivolumab Treatment for Non-Small Cell Lung Cancer. 査読 国際誌

    Kenji Takada, Keiichi Fujiwara, Eri Ando, Kiriko Onishi, Tadahiro Kuribayashi, Sho Mitsumune, Yuki Takigawa, Hiroaki Matsuura, Hiromi Watanabe, Kenichiro Kudo, Akiko Sato, Ken Sato, Takuo Shibayama

    Case reports in oncology   14 ( 2 )   792 - 796   2021年

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    We report the case of a 54-year-old man who was treated with nivolumab for recurrent squamous cell lung cancer. After 7 cycles of nivolumab treatment, the patient presented to our hospital with right eye vision loss. Gadolinium-enhanced magnetic resonance imaging of the brain showed enhancement around the optic nerve sheath. This finding and his symptoms led to the diagnosis of optic perineuritis (OPN). Steroid pulse therapy was administered twice although there was no remarkable improvement in his visual field defect. The relationship between OPN and nivolumab is unclear. However, immune-related adverse events caused by immune checkpoint inhibitors should be considered.

    DOI： 10.1159/000516275

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  • Combined Hypertrophic Pachymeningitis and Cerebral Venous Thrombosis in a Case of Granulomatosis with Polyangiitis. 査読 国際誌

    Tadahiro Kuribayashi, Yasuhiro Manabe, Shunya Fujiwara, Yoshio Omote, Hisashi Narai, Koji Abe

    Case reports in neurology   11 ( 2 )   252 - 255   2019年

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    担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

    We report a rare case of hypertrophic pachymeningitis (HP) and cerebral venous thrombosis associated with proteinase-3-antineutrophil cytoplasmic antibody (PR3-ANCA)-positive granulomatosis with polyangiitis (GPA). A 58-year-old male developed left headache after exudative otitis media. The laboratory data were positive for PR3-ANCA. Brain magnetic resonance imaging revealed bilateral paranasal sinusitis, left frontal lobe edema, and a thick dura mater with abnormal enhancement in the frontotemporal lobe. Magnetic resonance venography detected stenosis of the superior sagittal sinus. The patient was successfully treated with glucocorticoid, cyclophosphamide, and apixaban. Contrast neuroimaging should be performed for patients who present with unexplained headache, especially with middle ear and paranasal inflammation. These symptoms should be considered as GPA-related HP and cerebral venous thrombosis.

    DOI： 10.1159/000502284

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MISC

  • EGFR変異肺癌マウスモデルにおける腫瘍微小環境の空間的プロファイル解析

    大川祥, 冨田秀太, 栗林忠弘, 西村淳, 二宮貴一朗, 槇本剛, 頼冠名, 市原英基, 堀田勝幸, 田端雅弘, 前田嘉信, 木浦勝行, 大橋圭明

    日本肺癌学会学術集会号(CD-ROM)   65th   2024年

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  • NintedanibはOsimertinibが誘導する抗腫瘍免疫を賦活化する

    栗林忠弘, 西村淳, 大川祥, 槇本剛, 二宮貴一朗, 頼冠名, 市原英基, 堀田勝幸, 田端雅弘, 前田嘉信, 木浦勝行, 大橋圭明

    日本肺癌学会学術集会号(CD-ROM)   65th   2024年

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  • 非小細胞肺癌に対する免疫療法の効果予測におけるS100A8/A9の有用性の検討

    栗林忠弘, 木下理恵, 二宮貴一朗, 槇本剛, 久保寿夫, 頼冠名, 市原英基, 堀田勝幸, 田端雅弘, 前田嘉信, 木浦勝行, 豊岡伸一, 阪口政清, 大橋圭明

    日本肺癌学会学術集会号(CD-ROM)   65th   2024年

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  • ALK融合遺伝子変異陽性非小細胞肺癌におけるアレクチニブ早期耐性患者の特徴の検討

    栗林忠弘, 栗林忠弘, 槇本剛, 槇本剛, 冨田秀太, 井上博文, 二宮貴一朗, 二宮貴一朗, 横山俊秀, 久山彰一, 加藤有加, 工藤健一郎, 堀田尚克, 萱谷紘枝, 井上政昭, 杉本啓介, 大橋圭明, 大橋圭明, 堀田勝幸, 堀田勝幸

    日本肺癌学会学術集会号(CD-ROM)   65th   2024年

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  • ALK融合遺伝子変異陽性非小細胞肺癌におけるアレクチニブ早期耐性患者の臨床的特徴を明らかにするための後ろ向きコホート研究

    横山俊秀, 栗林忠弘, 槇本剛, 久山彰一, 加藤有加, 工藤健一郎, 堀田尚克, 萱谷紘枝, 井上政昭, 杉本啓介, 大橋圭明, 堀田勝幸

    日本呼吸器学会誌(Web)   13   2024年

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  • OsimertinibとADU-S100併用によるEGFR肺癌に対する抗腫瘍免疫効果

    西村淳, 栗林忠弘, 田岡征高, 大川祥, 中須賀崇匡, 平生敦子, 槇本剛, 二宮貴一朗, 市原英基, 頼冠名, 堀田勝幸, 田端雅弘, 前田嘉信, 木浦勝行, 大橋圭明

    日本肺癌学会学術集会号(CD-ROM)   65th   2024年

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  • Egfr改変肺癌マウスモデルを用いたosimertinibとnintedanibによる抗腫瘍効果の検討

    栗林忠弘, 田岡征高, 西村淳, 大川祥, 平生敦子, 中須賀崇匡, 森田絢子, 西達也, 槇本剛, 二宮貴一朗, 藤井昌学, 頼冠名, 市原英基, 堀田勝幸, 田端雅弘, 前田嘉信, 木浦勝行, 大橋圭明

    日本肺癌学会学術集会号(CD-ROM)   64th   2023年

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  • Egfr肺癌に対しADU-S100はosimertinibが誘導する抗腫瘍免疫を増強する

    西村淳, 田岡征高, 栗林忠弘, 大川祥, 中須賀崇匡, 平生敦子, 槇本剛, 二宮貴一朗, 藤井昌学, 頼冠名, 市原英基, 堀田勝幸, 田端雅弘, 前田嘉信, 木浦勝行, 大橋圭明

    日本肺癌学会学術集会号(CD-ROM)   64th   2023年

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  • EGFR変異陽性肺癌に対するAd-SGE-REICと抗PD-1抗体併用による抗腫瘍免疫賦活効果

    中須賀崇匡, 大橋圭明, 西井和也, 平生敦子, 大川祥, 高田健二, 西村淳, 栗林忠弘, 安東千裕, 西達也, 森田絢子, 槇本剛, 二宮貴一朗, 藤井昌学, 市原英基, 堀田勝幸, 田端雅弘, 前田嘉信, 木浦勝行

    日本肺癌学会学術集会号(CD-ROM)   63rd   2022年

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  • CD8陽性細胞抵抗性Egfr肺癌に対するSTING agonistによる抗腫瘍免疫の誘導

    西村淳, 大橋圭明, 栗林忠弘, 森田絢子, 西達也, 大川祥, 高田健二, 安東千裕, 中須賀崇匡, 西井和也, 平生敦子, 二宮貴一朗, 槇本剛, 藤井昌学, 市原英基, 堀田勝幸, 田端雅弘, 前田嘉信, 木浦勝行

    日本肺癌学会学術集会号(CD-ROM)   63rd   2022年

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  • 大量喀血に対して気管支動脈塞栓術と気管支充填術が奏効したALK陽性肺癌の1例

    藤岡佑輔, 田岡征高, 槇本剛, 栗林忠弘, 松浦宏昌, 下西惇, 二宮貴一朗, 肥後寿夫, 久保寿夫, 大橋圭明, 堀田勝幸, 宮原信明, 田端雅弘, 木浦勝行

    気管支学   44   2022年

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  • osimertinibが誘導する抗腫瘍免疫はM2マクロファージの抑制により増強される

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