" /> 【特別寄稿】免疫チェックポイント阻害薬とマイクロバイオーム■マイクロバイオームと発癌■宮永晃彦 |
呼吸臨床

【特別寄稿】免疫チェックポイント阻害薬とマイクロバイオーム

企画:久保田馨


 腸内細菌叢の変化が消化管のみならず、様々な全身疾患の発症リスクに関与するとの報告がなされている。免疫チェックポイント阻害薬(ICI)が肺がん薬物療法の大きな柱になってきた。腸管の無菌状態や抗生剤を投与されたマウスではICIの有効性が消失することや、臨床においても抗生剤を投与されていた患者群でのICIの有効性が低下することが報告されている。マイクロバイオームとICIに関する理解を深める目的で寄稿をいただいた。

マイクロバイオームと発癌

宮永晃彦*

*日本医科大学大学院医学研究科呼吸器内科分野(〒113-8602  東京都文京区千駄木1-1-5)


Microbiome and carcinogenesis

Akihiko Miyanaga*

*Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo


Keywords:マイクロバイオーム,肺癌,発癌,16S rRNA遺伝子,免疫チェックポイント阻害薬/microbiome,lung cancer,carcinogenesis,16S rRNA genes,immune checkpoint inhibitor


呼吸臨床 2020年4巻1号 論文No.e00094
Jpn Open J Respir Med 2020 Vol.4 No.1  Article No.e00094

DOI: 10.24557/kokyurinsho.4.e00094


掲載日:2020年1月14日


©️Akihiko Miyanaga. 本論文の複製権,翻訳権,上映権,譲渡権,貸与権,公衆送信権(送信可能化権を含む)は弊社に帰属し,それらの利用ならびに許諾等の管理は弊社が行います。


要旨

 マイクロバイオームは肥満,炎症性腸疾患,関節炎などでの研究が進んでおり,がん領域においても大腸癌と特定の細菌叢との関連性の研究が進んでいる。近年,16SリボソームRNA遺伝子解析やメタゲノム解析などの遺伝子解析の進歩により下気道のマイクロバイオームの検出が可能となり,肺癌においても発癌に関与する可能性のある細菌叢が報告されている。これらは新たな診断や治療のバイオマーカーとして,個別化医療に寄与する可能性がある。

文献

  1. Hilty M, et al. Disordered microbial communities in asthmatic airways. PLoS One. 2010; 5: e8578.
  2. Turnbaugh PJ, et al. The human microbiome project. Nature. 2007; 449: 804-10.
  3. Huang YJ, et al. The role of the lung microbiome in health and disease. A National Heart, Lung, and Blood Institute workshop report. Am J Respir Crit Care Med. 2013; 187: 1382-7.
  4. Heijink IH, et al. Cigarette smoke impairs airway epithelial barrier function and cell-cell contact recovery. Eur Respir J. 2012; 39: 419-28.
  5. Ege MJ, et al. Exposure to environmental microorganisms and childhood asthma. N Engl J Med. 2011; 364: 701-9.
  6. Huang YJ, et al. Airway microbiota and bronchial hyperresponsiveness in patients with suboptimally controlled asthma. J Allergy Clin Immunol. 2011; 127: 372-81.
  7. Pragman AA, et al. The lung microbiome in moderate and severe chronic obstructive pulmonary disease. PLoS One. 2012; 7: e47305.
  8. Cabrera-Rubio R, et al. Microbiome diversity in the bronchial tracts of patients with chronic obstructive pulmonary disease. J Clin Microbiol. 2012; 50: 3562-8.
  9. Yoshimoto S, et al. Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature. 2013; 499: 97-101.
  10. Castellarin M, et al. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res. 2012; 22: 299-306.
  11. Tahara T, et al. Fusobacterium in colonic flora and molecular features of colorectal carcinoma. Cancer Res. 2014; 74: 1311-8.
  12. Kostic AD, et al. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res. 2012; 22: 292-8.
  13. Kostic AD, et al. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe. 2013; 14: 207-15.
  14. Rubinstein MR, et al. Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/beta-catenin signaling via its FadA adhesin. Cell Host Microbe. 2013; 14: 195-206.
  15. Gur C, et al. Binding of the Fap2 protein of Fusobacterium nucleatum to human inhibitory receptor TIGIT protects tumors from immune cell attack. Immunity. 2015; 42: 344-55.
  16. Shiels MS, et al. Increased risk of lung cancer in men with tuberculosis in the alpha-tocopherol, beta-carotene cancer prevention study. Cancer Epidemiol Biomarkers Prev. 2011; 20: 672-8.
  17. Lee SH, et al. Characterization of microbiome in bronchoalveolar lavage fluid of patients with lung cancer comparing with benign mass like lesions. Lung Cancer. 2016; 102: 89-95.
  18. Yan X, et al. Discovery and validation of potential bacterial biomarkers for lung cancer. Am J Cancer Res. 2015; 5: 3111-22.
  19. Tsay JJ, et al. Airway microbiota is associated with upregulation of the PI3K pathway in lung cancer. Am J Respir Crit Care Med. 2018; 198: 1188-98.
  20. Greathouse KL, et al. Interaction between the microbiome and TP53 in human lung cancer. Genome Biol. 2018; 19: 123.
  21. Jin J, et al. Diminishing microbiome richness and distinction in the lower respiratory tract of lung cancer patients: A multiple comparative study design with independent validation. Lung Cancer. 2019; 136: 129-35.
  22. Liu Y, et al. Lung tissue microbial profile in lung cancer is distinct from emphysema. Am J Cancer Res. 2018; 8: 1775-87.
  23. Huang D, et al. The characterization of lung microbiome in lung cancer patients with different clinicopathology. Am J Cancer Res. 2019; 9: 2047-63.
  24. Gomes S, et al. Profiling of lung microbiota discloses differences in adenocarcinoma and squamous cell carcinoma. Sci Rep. 2019; 9: 12838.
  25. Sivan A, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015; 350: 1084-9.
  26. Vetizou M, et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science. 2015; 350: 1079-84.
  27. Routy B, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 2018; 359: 91-7.