Enhanced adaptive immune responses in lung adenocarcinoma through natural killer cell stimulation
Name
17460.full.pdf
Description
Published version
Size
2.03 MB
Format
Adobe PDF
Checksum (MD5)
1eac0f4b9710b0040147fa0e74a4106f
Author(s)
Schmidt, Leah Marie
Eskiocak, Banu
Kohn, Ryan
Dang, Celeste
Joshi, Nikhil
DuPage, Michel J.
Lee, Da-Yae
Jacks, Tyler E
Date Issued
August 2019
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Citation
Schmidt, Leah et al. "Enhanced adaptive immune responses in lung adenocarcinoma through natural killer cell stimulation." Proceedings of the National Academy of Sciences 116, 35 (August 2019): 17460-17469 © 2019 National Academy of Sciences
Version
Final published version
Abstract
Natural killer (NK) cells inhibit tumor development in mouse models and their presence in tumors correlates with patient survival. However, tumor-associated NK cells become dysfunctional; thus, stimulation of NK cells in cancer is emerging as an attractive immunotherapeutic strategy. In a mouse model of lung adenocarcinoma, NK cells localized to tumor stroma with immature phenotypes and low functional capacity. To test their responsiveness within established disease,we engineered a system for inducible expression of activating ligands in tumors. After stimulation, NK cells localized inside tumors, with increased cytokine production capacity. Strikingly, T cells were also recruited to tumors in an NK cell-dependent manner, and exhibited higher functionality. In neoantigen-expressing tumors, NK cell stimulation enhanced the number and function of tumor-specific T cells and, in long-term settings, reduced tumor growth. Thus, even in established disease NK cells can be activated to contribute to antitumor immunity, supporting their potential as an important target in cancer immunotherapy.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1073/pnas.1904253116
