Functional visualization of NK Cell-mediated killing of metastatic single tumor cells

• Ichise, Hiroshi

  Research Center for Dynamic Living Systems, Graduate School of Biostudies, Kyoto University

• Tsukamoto, Shoko

  Research Center for Dynamic Living Systems, Graduate School of Biostudies, Kyoto University

• Hirashima, Tsuyoshi

  Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University

• Konishi, Yoshinobu

  Research Center for Dynamic Living Systems, Graduate School of Biostudies, Kyoto University

• Oki, Choji

  Department of Nanopharmaceutical Sciences, Nagoya Institute of Technology

• Tsukiji, Shinya

  Department of Nanopharmaceutical Sciences, Nagoya Institute of Technology

• Iwano, Satoshi

  Brain Science Institute, Center for Brain Science, RIKEN

• Miyawaki, Atsushi

  Brain Science Institute, Center for Brain Science, RIKEN

• Sumiyama, Kenta

  Laboratory for Mouse Genetic Engineering, RIKEN Center for Biosystems Dynamics Research

• Terai, Kenta

  Research Center for Dynamic Living Systems, Graduate School of Biostudies, Kyoto University

• Matsuda, Michiyuki

  Research Center for Dynamic Living Systems, Graduate School of Biostudies, Kyoto University; Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University; Institute for Integrated Cell-Material Sciences, Kyoto University

Abstract

Natural killer (NK) cells lyse invading tumor cells to limit metastatic growth in the lung, but how some cancers evade this host protective mechanism to establish a growing lesion is unknown. Here we have combined ultra-sensitive bioluminescence imaging with intravital two-photon microscopy involving genetically-encoded biosensors to examine this question. NK cells eliminated disseminated tumor cells from the lung within 24 hrs of arrival, but not thereafter. Intravital dynamic imaging revealed that 50% of NK-tumor cell encounters lead to tumor cell death in the first 4 hrs after tumor cell arrival, but after 24 hrs of arrival, nearly 100% of the interactions result in the survival of the tumor cell. During this 24 hrs period, the probability of ERK activation in NK cells upon encountering the tumor cells was decreased from 68% to 8%, which correlated with the loss of the activating ligand CD155/PVR/Necl5 from the tumor cell surface. Thus, by quantitatively visualizing the NK-tumor cell interaction at the early stage of metastasis, we have revealed the crucial parameters of NK cell immune surveillance in the lung.

Journal

• eLife

  eLife 11 2022

  eLife Sciences Publications, Ltd

Keywords

• natural killer cells
• tumor immunology
• lung metastasis
• circulating tumor cell
• intravital imaging
• genetically encoded biosensor
• thrombin

Details

• CRID: 1050009683079834752
• NII Article ID: 120007191378
• DOI: 10.7554/elife.76269
• ISSN: 2050084X
• HANDLE: 2433/267925
• Web Site: https://cdn.elifesciences.org/articles/76269/elife-76269-v2.pdf
• Web Site: https://cdn.elifesciences.org/articles/76269/elife-76269-v2.xml
• Web Site: https://elifesciences.org/articles/76269
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN