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The changing role of natural killer cells in cancer metastasis
Isaac S. Chan, Andrew J. Ewald
Isaac S. Chan, Andrew J. Ewald
Published March 15, 2022
Citation Information: J Clin Invest. 2022;132(6):e143762. https://doi.org/10.1172/JCI143762.
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Review

The changing role of natural killer cells in cancer metastasis

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Abstract

Natural killer (NK) cells are innate immune cells that are critical to the body’s antitumor and antimetastatic defense. As such, novel therapies are being developed to utilize NK cells as part of a next generation of immunotherapies to treat patients with metastatic disease. Therefore, it is essential for us to examine how metastatic cancer cells and NK cells interact with each other throughout the metastatic cascade. In this Review, we highlight the recent body of work that has begun to answer these questions. We explore how the unique biology of cancer cells at each stage of metastasis alters fundamental NK cell biology, including how cancer cells can evade immunosurveillance and co-opt NK cells into cells that promote metastasis. We also discuss the translational potential of this knowledge.

Authors

Isaac S. Chan, Andrew J. Ewald

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Figure 2

Signaling interactions between NK cells and cancer cells in the tumor microenvironment.

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Signaling interactions between NK cells and cancer cells in the tumor mi...
Natural killer cells within the tumor microenvironment are governed by a series of signals from cancer cells and from other immune cells that are present. During metastasis, exposure to cancer cells can alter these signals to activate or inactivate the NK cells or alter them toward a tumor-promoting phenotype.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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