Functional visualization of NK Cell-mediated killing of metastatic single tumor cells
- Kyoto University, Japan
- Nagoya Institute of Technology, Japan
- RIKEN, Japan
- RIKEN Center for Biosystems Dynamics Research, Japan
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.
Data availability
Imaging data are deposited at SSBD: database (https://doi.org/10.24631/ssbd.repos.2021.08.001).
Article and author information
Author details
Tsuyoshi Hirashima
Funding
Japan Society for the Promotion of Science (18K15317)
- Hiroshi Ichise
Japan Society for the Promotion of Science (15H05949)
- Michiyuki Matsuda
Japan Society for the Promotion of Science (19H00993)
- Michiyuki Matsuda
Japan Agency for Medical Research and Development (19gm5010003h0003)
- Michiyuki Matsuda
Fugaku Trust for Medicinal Research
- Michiyuki Matsuda
Core Research for Evolutional Science and Technology (JPMJCR1654)
- Michiyuki Matsuda
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: The animal protocols were reviewed and approved by the Animal Care and Use Committee of Kyoto University Graduate School of Medicine (approval no. 19090)
Copyright
© 2022, Ichise et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Functional visualization of NK Cell-mediated killing of metastatic single tumor cells
eLife 11:e76269.
https://doi.org/10.7554/eLife.76269
