徳島大学 / 教育研究者総覧 --- 塚﨑佑貴

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徳島大学 ⟩ 大学院医歯薬学研究部 ⟩ 医学域 ⟩ 連携研究部門(医学域) ⟩ 寄附講座系(医学域) ⟩ 地域総合医療学 ⟩

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研究活動

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研究テーマ

著書・論文

学術論文(審査論文):

1.	Yohei Yabuki, Atsushi Mitsuhashi, Hirokazu Ogino, Aito Yoshida, Thi Na Nguyen, Hiroto Yoneda, Ryohiko Ozaki, Yuki Tsukazaki, Yutaka Morita, Hiroshi Nokihara, Seidai Satou, Tsutomu Shinohara, Masaki Hanibuchi and Yasuhiko Nishioka : Hypoxia-inducible factor-targeting therapy augmented the sensitivity to programmed death ligand-1 blockade by enhancing interferon-γ-induced chemokines in tumor cells, International Journal of Cancer, 156, 9, 1814-1825, 2024. (要約) Immune checkpoint inhibitors (ICIs) targeting programmed death ligand-1 (PD-L1) provide clinical benefits for various advanced malignancies. However, the predictive factors that determine sensitivity to ICIs have not been fully elucidated. We focused on tumor-derived CXCL10/11 as a pivotal factor that determines the response to PD-L1 blockade by regulating T cell accumulation and tumor angiogenesis. We previously reported that CXCL10/11 was upregulated by interferon (IFN)-γ in ICI-sensitive tumor cells but not in ICI-resistant cells, including mouse Lewis lung carcinoma (LLC). In the present study, gene silencing of tumor-derived CXCL10/11 induced resistance to PD-L1 blockade in AB1-HA mesothelioma cell-bearing mice. To identify the mechanisms underlying ICI resistance, we performed a microarray analysis to compare the IFN-γ-inducible genes between ICI-sensitive AB1-HA and ICI-resistant LLC in vitro. A pathway analysis based on microarray data indicated that hypoxia-inducible factor (HIF) 1A is the key signal that inhibits CXCL10/11 expression. We revealed that the HIF1A inhibitors echinomycin (EC) and YC-1 upregulated CXCL10/11 genes induced by IFN-γ in tumor cells in vitro. In addition, combination therapy with PD-L1 blockade and EC demonstrated synergistic antitumor effects in LLC-bearing mice. Combination therapy enhanced tumor infiltration of CD8 T cells and suppressed tumor angiogenesis. The present study suggests that HIF1A signaling in tumor cells dominates ICI resistance via the downregulation of tumor-derived CXCL10/11. (キーワード) angiogenesis / CXCL10/11 / HIF1A / immune checkpoint inhibitor / interferon-γ (出版サイトへのリンク) ● Publication site (DOI): 10.1002/ijc.35301 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 39686841 ● Summary page in Scopus @ Elsevier: 2-s2.0-85212305972 (DOI: 10.1002/ijc.35301, PubMed: 39686841, Elsevier: Scopus)
2.	Yuki Tsukazaki, Hirokazu Ogino, Yoshio Okano, Soji Kakiuchi, Shoko Harada, Yuko Toyoda, Yugo Matsumura, Seiya Ichihara, Takeshi Imakura, Rikako Matsumoto, Ryohiko Ozaki, Ei Ogawa, Yutaka Morita, Atsushi Mitsuhashi, Yohei Yabuki, Hiroto Yoneda, Masaki Hanibuchi, Kayoko Hase, Eiji Takeuchi, Takashi Haku and Yasuhiko Nishioka : Granulocyte colony-stimulating factor has the potential to attenuate the therapeutic efficacy of chemo-immunotherapy for extensive-stage small-cell lung cancer, International Journal of Clinical Oncology, 29, 10, 1451-1460, 2024. (要約) Granulocyte colony-stimulating factor (G-CSF) has the potential to attenuate the anti-tumor immune responses of T-cells by increasing immune suppressive neutrophils and myeloid-derived suppressor cells. However, the clinical impact of G-CSF on the efficacy of immunotherapy remains unknown. This multi-center retrospective analysis evaluated the impact of G-CSF in patients with extensive-stage small-cell lung cancer (ES-SCLC) treated with chemo-immunotherapy. We analyzed 65 patients with ES-SCLC who completed four cycles of induction chemo-immunotherapy and evaluated the effects of G-CSF on progression-free survival (PFS), overall survival (OS), and a durable response to immunotherapy (defined as PFS 12 months). Fifty patients (76.9%) received 1 dose of G-CSF. The PFS of the patients with G-CSF was poorer than that of the patients without G-CSF (median PFS 8.3 vs. 4.9 months, p = 0.009). The OS of the patients with G-CSF tended to be shorter, but not statistically significant, than that of the patients without G-CSF (median OS 24.3 vs. 16.4 months, p = 0.137). In the multivariate analysis, G-CSF administration was associated with poorer PFS (hazard ratio 2.78, 95% CI 1.36-5.69, p = 0.005) and was identified as a determinant of a durable response (odds ratio 0.18, 95% CI 0.04-0.80, p = 0.024). These results were consistent with other definitions of G-CSF administration (administration of 1 dose of pegfilgrastim, or either 5 doses of filgrastim or 1 dose of pegfilgrastim). G-CSF has the potential to attenuate the efficacy of immunotherapy; therefore, the indication for G-CSF during chemo-immunotherapy should be carefully considered for ES-SCLC. (キーワード) Chemo-immunotherapy / Extensive-stage small-cell lung cancer / Granulocyte colony-stimulating factor (出版サイトへのリンク) ● Publication site (DOI): 10.1007/s10147-024-02586-0 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 39009900 ● Summary page in Scopus @ Elsevier: 2-s2.0-85198503607 (DOI: 10.1007/s10147-024-02586-0, PubMed: 39009900, Elsevier: Scopus)
3.	Hiroyuki Kozai, Hirokazu Ogino, Atsushi Mitsuhashi, Thi Na Nguyen, Yuki Tsukazaki, Yohei Yabuki, Ryohiko Ozaki, Hiroto Yoneda, Seidai Satou, Masaki Hanibuchi, Tsutomu Shinohara, Hiroshi Nokihara and Yasuhiko Nishioka : Potential of fluoropyrimidine to be an immunologically optimal partner of immune checkpoint inhibitors through inducing immunogenic cell death for thoracic malignancies., Thoracic Cancer, 15, 5, 369-378, 2024. (要約) 5-FU induced cell surface expression of CRT and ATP secretion most efficiently among the several chemotherapeutic agents. This effect was enhanced when it was combined with platinum. In the antitumor vaccination assay in vivo, we found that vaccination with dying-AB1-HA (a murine malignant mesothelioma cell line) cells treated with 5-FU, but neither PEM nor PTX, reduced the tumor growth of living-AB1-HA cells inoculated 1 week after vaccination by recruiting CD3 (キーワード) Humans / Animals / Mice / Carcinoma, Non-Small-Cell Lung / Immune Checkpoint Inhibitors / CD8-Positive T-Lymphocytes / Platinum / Immunogenic Cell Death / Lung Neoplasms / Pemetrexed / Antimetabolites / Cell Line, Tumor / Taxoids / Fluorouracil / Adenosine Triphosphate / Tumor Microenvironment (徳島大学機関リポジトリ) ● Metadata: 2012077 (出版サイトへのリンク) ● Publication site (DOI): 10.1111/1759-7714.15200 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 38146645 ● Search Scopus @ Elsevier (PMID): 38146645 ● Search Scopus @ Elsevier (DOI): 10.1111/1759-7714.15200 (徳島大学機関リポジトリ: 2012077, DOI: 10.1111/1759-7714.15200, PubMed: 38146645)
4.	Kenya Miyamoto, Hirokazu Ogino, Takumi Kakimoto, Yugo Matsumura, Keiko Haji, Atsushi Mitsuhashi, Yutaka Morita, Yuki Tsukazaki, Yohei Yabuki, Ryohiko Ozaki, Hiroto Yoneda, Seidai Satou, Masaki Hanibuchi, Yoshimi Bando, Hiroshi Nokihara and Yasuhiko Nishioka : Transformation of epidermal growth factor receptor mutated lung adenocarcinoma to small-cell carcinoma long after the cessation of tyrosine kinase inhibitor treatment: A case series and literature review, Respiratory Medicine Case Reports, 51, 102076, 2024. (キーワード) Acquired resistance / Epidermal growth factor receptor / Non-small-cell lung cancer / Small-cell lung cancer transformation / Tyrosine kinase inhibitors (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.rmcr.2024.102076 (文献検索サイトへのリンク) ● Summary page in Scopus @ Elsevier: 2-s2.0-85196709618 (DOI: 10.1016/j.rmcr.2024.102076, Elsevier: Scopus)
5.	Hiroki Takahashi, Hirokazu Ogino, Hiroki Bando, Atsushi Mitsuhashi, Yuki Tsukazaki, Yohei Yabuki, Ryohiko Ozaki, Hiroto Yoneda, Seidai Satou, Masaki Hanibuchi and Yasuhiko Nishioka : FoundationOne CDx detected an uncovered variant of epidermal growth factor receptor exon 19 deletion by Oncomine Dx target test in a patient with lung adenocarcinoma., Respiratory Medicine Case Reports, 45, 101893, 2023. (徳島大学機関リポジトリ) ● Metadata: 2012094 (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.rmcr.2023.101893 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37485237 ● Search Scopus @ Elsevier (PMID): 37485237 ● Search Scopus @ Elsevier (DOI): 10.1016/j.rmcr.2023.101893 (徳島大学機関リポジトリ: 2012094, DOI: 10.1016/j.rmcr.2023.101893, PubMed: 37485237)

国際会議:

1.	Yuki Tsukazaki, Hirokazu Ogino, Yoshio Okano, Soji Kakiuchi, Shoko Harada, Yuko Toyoda, Yugo Matsumura, Seiya Ichihara, Takeshi Imakura, Rikako Matsumoto, Ryohiko Ozaki, Ei Ogawa, Yutaka Morita, Atsushi Mitsuhashi, Yohei Yabuki, Hiroto Yoneda, Masaki Hanibuchi, Kayoko Hase, Eiji Takeuchi, Takashi Haku and Yasuhiko Nishioka : The Conflicting Impacts of G-CSF on the Therapeutic Efficacy of Chemoimmunotherapy for Extensive Stage Small Cell Lung Cancer, 2024 World Conference on Lung Cancer, San Diego, Sep. 2024.
2.	Hirokazu Ogino, Na Thi Nguyen, Hiroyuki Kozai, Atsushi Mitsuhashi, Yuki Tsukazaki, Yohei Yabuki, Ryohiko Ozaki, Hiroshi Nokihara, Masaki Hanibuchi and Yasuhiko Nishioka : The potential of fluoropyrimidine to be an immunologically optimal partner of immunotherapy for thoracic malignancies, 2024 World Conference on Lung Cancer, San Diego, Sep. 2024.

国内講演発表:

1.	塚﨑佑貴, 荻野広和, 岡野義夫, 柿内聡司, 豊田優子, 松本利加子, 尾崎領彦, 森田優, 三橋惇志, 矢葺洋平, 埴淵昌毅, 長谷加容子, 竹内栄治, 葉久貴司, 西岡安彦 : G-CSFが進展型小細胞肺癌における化学免疫療法の治療効果に及ぼす影響を検討した多施設共同後方視的解析, 第65回日本肺癌学会学術集会, 2024年11月.
2.	矢葺洋平, 三橋惇志, 荻野広和, 尾崎領彦, 塚﨑佑貴, 埴淵昌毅, 西岡安彦 : IFN-γ反応性ケモカイン産生制御機序の解明と新規複合がん免疫療法への応用, 第65回日本肺癌学会学術集会, 2024年11月.
3.	三橋惇志, 荻野広和, 矢葺洋平, 尾崎領彦, 塚﨑佑貴, 埴淵昌毅, 軒原浩, 西岡安彦 : Fibrocyte 分化制御による免疫排除克服と新規複合がん免疫療法への展開, 第65回日本肺癌学会学術集会, 2024年10月.
4.	塚﨑佑貴, 荻野広和, 岡野義夫, 柿内聡司, 豊田優子, 松本利加子, 尾崎領彦, 森田優, 三橋惇志, 矢葺洋平, 埴淵昌毅, 長谷加容子, 竹内栄治, 葉久貴司, 西岡安彦 : G-CSF が進展型小細胞肺癌に対する化学免疫療法の治療効果に及ぼす影響に関する解析, 第62回日本癌治療学会学術集会, 2024年10月.
5.	三橋惇志, 小山壱也, 荻野広和, 矢葺洋平, 尾崎領彦, 塚﨑佑貴, 森田優, 吉田碧人, 軒原浩, 埴淵昌毅, 西岡安彦 : Fibrocyte 制御によるがん免疫排除克服に向けた治療戦略, 第83回日本癌学会学術総会, 2024年9月.
6.	塚﨑佑貴, 飛梅亮, 三橋惇志, 尾崎領彦, 矢葺洋平, 米田浩人, 荻野広和, 埴淵昌毅, 小川博久, 滝沢宏光, 西岡安彦 : 線維細胞の腫瘍内浸潤およびそれを誘導する走化因子が非小細胞肺癌の予後に及ぼす影響についての解析, 第64回日本呼吸器学会学術講演会, 2024年4月.
7.	荻野広和, Nguyen Thi Na, 香西博之, 三橋惇志, 塚﨑佑貴, 矢葺洋平, 尾崎領彦, 埴淵昌毅, 西岡安彦 : 胸部腫瘍に対して免疫チェックポイント阻害薬と併用すべき至適抗がん剤の同定を目指した免疫学的解析, 第64回日本呼吸器学会学術講演会, 2024年4月.
8.	Yuki Tsukazaki, Hirokazu Ogino, Yoshio Okano, Soji Kakiuchi, Shoko Harada, Yugo Matumura, Seiya Ichihara, Takeshi Imakura, Ryohiko Ozaki, Ei Ogawa, Yutaka Morita, Atsushi Mitsuhashi, Yohei Yabuki, Hiroto Yoneda, Masaki Hanibuchi, Yuko Toyoda, Kayoko Hase, Eiji Takeuchi, Takashi Haku and Yasuhiko Nishioka : The impacts of G-CSF on the therapeutic efficacy of chemo-immunotherapy for extensive-stage small cell lung cancer., 2024 the Japanese Society of Medical Oncology Annual Meeting (JSMO2024), Feb. 2024.
9.	Hirokazu Ogino, Nguyen Na Thi, Hiroyuki Kozai, Atsushi Mitsuhashi, Yuki Tsukazaki, Yohei Yabuki, Ryohiko Ozaki, Hiroshi Nokihara, Masaki Hanibuchi and Yasuhiko Nishioka : Fluoropyrimidine has a potential to be an immunologically optimal partner ofimmunotherapy for thoracic malignancies., 2024 the Japanese Society of Medical Oncology Annual Meeting (JSMO2024), Feb. 2024.
10.	塚﨑佑貴, 飛梅亮, 三橋惇志, 尾崎領彦, 矢葺洋平, 米田浩人, 荻野広和, 埴淵昌毅, 小川博久, 滝沢宏光, 西岡安彦 : 非小細胞肺癌症例における腫瘍浸潤線維細胞の走化因子と疾患予後との関連性についての解析, 第64回日本肺癌学会学術集会, 2023年11月.
11.	荻野広和, 香西博之, 三橋惇志, 塚﨑佑貴, 矢葺洋平, 尾崎領彦, 米田浩人, 埴淵昌毅, 軒原浩, 西岡安彦 : フッ化ピリミジンは胸部腫瘍の免疫原性細胞死を誘導し免疫チェックポイント阻害薬の至適併用薬となり得る, 第64回日本肺癌学会学術集会, 2023年11月.
12.	尾崎領彦, 軒原浩, 塚﨑佑貴, 矢葺洋平, 三橋惇志, 米田浩人, 荻野広和, 西岡安彦 : 進展型小細胞肺癌において2次治療が受けられない患者の臨床的背景の検討, 第64回日本肺癌学会学術集会, 2023年11月.
13.	矢葺洋平, 三橋惇志, 荻野広和, Na T. Nguyen, 米田浩人, 尾崎領彦, 塚﨑佑貴, 埴淵昌毅, 軒原浩, 西岡安彦 : HIF1A 阻害による腫瘍細胞由来 CXCL10/11 制御を介した抗 PDL1 抗体への耐性克服, 第82回日本癌学会学術総会, 2023年9月.
14.	塚﨑佑貴, 三橋惇志, 尾崎領彦, 矢葺洋平, 米田浩人, 荻野広和, 西岡安彦 : 肺癌における腫瘍浸潤線維細胞の走化因子とその疾患予後に及ぼす影響についての解析, 第27回日本がん分子標的治療学会学術集会, 2023年6月.