部門長小山は大阪大学大学院医学系研究科呼吸器免疫内科学の特任准教授を兼任しています。
（http://www.imed3.med.osaka-u.ac.jp/index.html）

キーワード

• 腫瘍免疫
• 免疫チェックポイント阻害剤

主な研究テーマ

• がん細胞の膜上に発現する分子による腫瘍免疫微小環境の修飾とそれらを標的とした治療法の開発
• 病態に基づく腫瘍浸潤骨髄球系細胞などの抑制性サブセットによる免疫抑制機構の解析　
• 免疫細胞浸潤が乏しいもしくは排除されたnon-inflamed 腫瘍に対する免疫賦活化誘導の検討

Email

skoyama●east.ncc.go.jp

（「●」記号を「@」記号に置き換えてください。）

略歴

• 2002年 東北大学医学部卒業
• 2009年 東北大学大学院医学系研究科博士課程修了
• 2009年 東北大学病院呼吸器内科 日本学術振興会特別研究員
• 2010年 Dana-Farber Cancer Institute, Research fellow
• 2014年 Dana-Farber Cancer Institute, Instructor
• 2015年 大阪大学大学院医学系研究科呼吸器免疫内科学 特任助教
• 2020年 国立がん研究センター 先端医療開発センター 免疫TR分野 ユニット長
• 2022年 大阪大学大学院医学系研究科 呼吸器免疫内科学/免疫分子制御学 特任准教授

主な所属学会

• 日本癌学会
• 日本免疫学会
• 日本がん免疫学会（評議員）
• 日本がん分子標的治療学会
• American Association for Cancer Research (AACR)
• 日本内科学会（総合内科専門医）
• 日本呼吸器学会（専門医、指導医）

主な論文

1. Hirai T, Naito Y, Koyama S^#, Nakanishi Y, Masuhiro K, Izumi M, Kuge T, Naito M, Mizuno Y, Yamaguchi Y, Kang S, Yaga M, Futami Y, Nojima S, Nishide M, Morita T, Kato Y, Tsuda T, Takemoto N, Kinugasa-Katayama Y, Aoshi T, Villa JK, Yamashita K, Enokida T, Hoshi Y, Matsuura K, Tahara M, Takamatsu H, Takeda Y, Inohara H, Kumanogoh A^#. Sema6D forward signaling impairs T cell activation and proliferation in head and neck cancer. JCI Insight. 2024 Feb 8;9(3):e166349.
2. Kumagai S, Koyama S^#, Shitara K^#. Precise patient stratification in esophageal cancer: Biomarkers for immunochemotherapy. Cancer Cell. 2023 Jul 10;41(7):1199-1201.
3. Naito Y, Koyama S^#, Masuhiro K, Hirai T, Uenami T, Inoue T, Osa A, Machiyama H, Watanabe G, Sax N, Villa J, Kinugasa-Katayama Y, Nojima S, Yaga M, Hosono Y, Okuzaki D, Satoh S, Tsuda T, Nakanishi Y, Suga Y, Morita T, Fukushima K, Nishide M, Shiroyama T, Miyake K, Iwahori K, Hirata H, Nagatomo I, Yano Y, Tamiya M, Kumagai T, Takemoto N, Inohara H, Yamasaki S, Yamashita K, Aoshi T, Akbay EA, Hosen N, Shintani Y, Takamatsu H, Mori M, Takeda Y, Kumanogoh A#. Tumor-derived semaphorin 4A improves PD-1-blocking antibody efficacy by enhancing CD8+ T cell cytotoxicity and proliferation. Sci Adv. 2023 May 19;9(20):eade0718.
4. Itahashi K, Irie T, Yuda J, Kumagai S, Tanegashima T, Lin YT, Watanabe S, Goto Y, Suzuki J, Aokage K, Tsuboi M, Minami Y, Ishii G, Ohe Y, Ise W, Kurosaki T, Suzuki Y, Koyama S, Nishikawa H. BATF epigenetically and transcriptionally controls the activation program of regulatory T cells in human tumors. Sci Immunol. 2022 Oct 14;7(76):eabk0957.
5. Kobayashi T, Kumagai S, Doi R, Afonina E, Koyama S, Nishikawa H. Isolation of tumor-infiltrating lymphocytes from preserved human tumor tissue specimens for downstream characterization. STAR Protoc. 2022 Sep 16;3(3):101557.
6. Masuhiro K, Tamiya M, Fujimoto K, Koyama S^#, Naito Y, Osa A, Hirai T, Suzuki H, Okamoto N, Shiroyama T, Nishino K, Adachi Y, Nii T, Kinugasa-Katayama Y, Kajihara A, Morita T, Imoto S, Uematsu S, Irie T, Okuzaki D, Aoshi T, Takeda Y, Kumagai T, Hirashima T, Kumanogoh A#. Bronchoalveolar lavage fluid reveals factors contributing to the efficacy of PD-1 blockade in lung cancer. JCI Insight. 2022 May 9;7(9):e157915.
7. Kumagai S, Koyama S^#, Itahashi K, Tanegashima T, Lin YT, Togashi Y, Kamada T, Irie T, Okumura G, Kono H, Ito D, Fujii R, Watanabe S, Sai A, Fukuoka S, Sugiyama E, Watanabe G, Owari T, Nishinakamura H, Sugiyama D, Maeda Y, Kawazoe A, Yukami H, Chida K, Ohara Y, Yoshida T, Shinno Y, Takeyasu Y, Shirasawa M, Nakama K, Aokage K, Suzuki J, Ishii G, Kuwata T, Sakamoto N, Kawazu M, Ueno T, Mori T, Yamazaki N, Tsuboi M, Yatabe Y, Kinoshita T, Doi T, Shitara K, Mano H, Nishikawa H^#. Lactic acid promotes PD-1 expression in regulatory T cells in highly glycolytic tumor microenvironments. Cancer Cell. 2022 Feb 14;40(2):201-218.e9.
8. Koyama S, Nishikawa H. Mechanisms of regulatory T cell infiltration in tumors: implications for innovative immune precision therapies. J Immunother Cancer. 2021 Jul;9(7):e002591.
9. Kumagai S, Koyama S, Nishikawa H. Antitumour immunity regulated by aberrant ERBB family signalling. Nat Rev Cancer. 2021 Mar;21(3):181-197.
10. Briones JC, Espulgar WV, Koyama S, Yoshikawa H, Park J, Naito Y, Kumanogoh A, Tamiya E, Takamatsu H, Saito M. A Microfluidic Platform for Single Cell Fluorometric Granzyme B Profiling. Theranostics. 2020 Jan 1;10(1):123-132.
11. Miret JJ, Kirschmeier P, Koyama S, Zhu M, Li YY, Naito Y, Wu M, Malladi VS, Huang W, Walker W, Palakurthi S, Dranoff G, Hammerman PS, Pecot CV, Wong KK, Akbay EA. Suppression of Myeloid Cell Arginase Activity leads to Therapeutic Response in a NSCLC Mouse Model by Activating Anti-Tumor Immunity. J Immunother Cancer. 2019 Feb 6;7(1):32.
12. Osa A, Uenami T, Koyama S^#, Fujimoto K, Okuzaki D, Takimoto T, Hirata H, Yano Y, Yokota S, Kinehara Y, Naito Y, Otsuka T, Kanazu M, Kuroyama M, Hamaguchi M, Koba T, Futami Y, Ishijima M, Suga Y, Akazawa Y, Machiyama H, Iwahori K, Takamatsu H, Nagatomo I, Takeda Y, Kida H, Akbay EA, Hammerman PS, Wong KK, Dranoff G, Mori M, Kijima T^#, Kumanogoh A^#. Clinical implications of monitoring nivolumab immunokinetics in non-small cell lung cancer patients. JCI Insight. 2018 Oct 4;3(19):e59125.
13. Chongsathidkiet P^*, Jackson C^*, Koyama S^*, Loebel F, Cui X, Farber SH, Woroniecka K, Elsamadicy AA, Dechant CA, Kemeny HR, Sanchez-Perez L, Cheema TA, Souders NC, Herndon JE, Coumans JV, Everitt JI, Nahed BV, Sampson JH, Gunn MD, Martuza RL, Dranoff G, Curry WT, Fecci PE. Sequestration of T cells in bone marrow in the setting of glioblastoma and other intracranial tumors. Nat Med. 2018 Aug;24(8):1143-1150.
14. Plant AS, Koyama S, Sinai C, Solomon IH, Griffin GK, Ligon KL, Bandopadhayay P, Betensky R, Emerson R, Dranoff G, Kieran MW, Ritz J. Immunophenotyping of pediatric brain tumors: correlating immune infiltrate with histology, mutational load, and survival and assessing clonal T cell response. J Neurooncol. 2018 Apr;137(2):269-278.
15. Akbay EA^*, Koyama S^*, Liu Y, Dries R, Bufe LE, Silkes M, Alam MM, Magee DM, Jones R, Jinushi M, Kulkarni M, Carretero J, Wang X, Warner-Hatten T, Cavanaugh JD, Osa A, Kumanogoh A, Freeman GJ, Awad MM, Christiani DC, Bueno R, Hammerman PS, Dranoff G, Wong KK. Interleukin-17A Promotes Lung Tumor Progression through Neutrophil Attraction to Tumor Sites and Mediating Resistance to PD-1 Blockade. J Thorac Oncol. 2017 Aug;12(8):1268-1279.
16. Herter-Sprie GS^*, Koyama S^*, Korideck H, Hai J, Deng J, Li YY, Buczkowski KA, Grant AK, Ullas S, Rhee K, Cavanaugh JD, Neupane NP, Christensen CL, Herter JM, Makrigiorgos GM, Hodi FS, Freeman GJ, Dranoff G, Hammerman PS, Kimmelman AC, Wong KK. Synergy of radiotherapy and PD-1 blockade in Kras-mutant lung cancer. JCI Insight. 2016 Jun 16;1(9):e87415.
17. Koyama S, Akbay EA, Li YY, Herter-Sprie GS, Buczkowski KA, Richards WG, Gandhi L, Redig AJ, Rodig SJ, Asahina H, Jones RE, Kulkarni MM, Kuraguchi M, Palakurthi S, Fecci PE, Johnson BE, Janne PA, Engelman JA, Gangadharan SP, Costa DB, Freeman GJ, Bueno R, Hodi FS, Dranoff G, Wong KK, Hammerman PS. Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints. Nat Commun. 2016 Feb 17;7時10分501.
18. Koyama S, Akbay EA, Li YY, Aref AR, Skoulidis F, Herter-Sprie GS, Buczkowski KA, Liu Y, Awad MM, Denning WL, Diao L, Wang J, Parra-Cuentas ER, Wistuba II, Soucheray M, Thai T, Asahina H, Kitajima S, Altabef A, Cavanaugh JD, Rhee K, Gao P, Zhang H, Fecci PE, Shimamura T, Hellmann MD, Heymach JV, Hodi FS, Freeman GJ, Barbie DA, Dranoff G, Hammerman PS, Wong KK. STK11/LKB1 Deficiency Promotes Neutrophil Recruitment and Proinflammatory Cytokine Production to Suppress T-cell Activity in the Lung Tumor Microenvironment. Cancer Res. 2016 Mar 1;76(5):999-1008.
19. Xu C, Fillmore CM, Koyama S, Wu H, Zhao Y, Chen Z, Herter-Sprie GS, Akbay EA, Tchaicha JH, Altabef A, Reibel JB, Walton Z, Ji H, Watanabe H, Jänne PA, Castrillon DH, Rustgi AK, Bass AJ, Freeman GJ, Padera RF, Dranoff G, Hammerman PS, Kim CF, Wong KK. Loss of Lkb1 and Pten leads to lung squamous cell carcinoma with elevated PD-L1 expression. Cancer Cell. 2014 May 12;25(5):590-604.
20. Akbay EA^*, Koyama S^*, Carretero J, Altabef A, Tchaicha JH, Christensen CL, Mikse OR, Cherniack AD, Beauchamp EM, Pugh TJ, Wilkerson MD, Fecci PE, Butaney M, Reibel JB, Soucheray M, Cohoon TJ, Janne PA, Meyerson M, Hayes DN, Shapiro GI, Shimamura T, Sholl LM, Rodig SJ, Freeman GJ, Hammerman PS, Dranoff G, Wong KK. Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors. Cancer Discov. 2013 Dec;3(12):1355-63.
21. Aoshi T, Koyama S, Kobiyama K, Akira S, Ishii KJ. Innate and adaptive immune responses to viral infection and vaccination. Curr Opin Virol. 2011 Oct;1(4):226-32.
22. Koyama S, Aoshi T, Tanimoto T, Kumagai Y, Kobiyama K, Tougan T, Sakurai K, Coban C, Horii T, Akira S, Ishii KJ. Plasmacytoid dendritic cells delineate immunogenicity of influenza vaccine subtypes. Sci Transl Med. 2010 Mar 31;2(25):25ra24.
23. Koyama S, Coban C, Aoshi T, Horii T, Akira S, Ishii KJ. Innate immune control of nucleic acid-based vaccine immunogenicity. Expert Rev Vaccines. 2009 Aug;8(8):1099-107.
24. Koyama S, Ishii KJ, Coban C, Akira S. Innate immune response to viral infection. Cytokine. 2008 Sep;43(3):336-41.
25. Ishii KJ, Koyama S, Nakagawa A, Coban C, Akira S. Host innate immune receptors and beyond: making sense of microbial infections. Cell Host Microbe. 2008 Jun 12;3(6):352-63.
26. Ishii KJ, Kawagoe T, Koyama S, Matsui K, Kumar H, Kawai T, Uematsu S, Takeuchi O, Takeshita F, Coban C, Akira S. TANK-binding kinase-1 delineates innate and adaptive immune responses to DNA vaccines. Nature. 2008 Feb 7;451(7179):725-9.
27. Kumar H^*, Koyama S^*, Ishii KJ, Kawai T, Akira S. Cutting Edge: Cooperation of IPS-1- and TRIF-Dependent Pathways in Poly IC-Enhanced Antibody Production and Cytotoxic T Cell Responses. J Immunol. 2008 Jan 15;180(2):683-7.
28. Koyama S, Ishii KJ, Kumar H, Tanimoto T, Coban C, Uematsu S, Kawai T, Akira S. Differential role of TLR- and RLR-signaling in the immune responses to influenza A virus infection and vaccination. J Immunol. 2007 Oct 1;179(7):4711-20.

その他

• 2012年　The Margaret A. Cunningham Immune Mechanisms in Cancer Research Fellowship Award
• 2017年　日本肺癌学会若手奨励賞
• 2022年　JCA (Japanese Cancer Association)-永山賞