Enhanced adaptive immune responses in lung adenocarcinoma through natural killer cell stimulation
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 mode...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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National Academy of Sciences
2020
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| Online Access: | https://hdl.handle.net/1721.1/125983 |
| _version_ | 1826200791974674432 |
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| author | Schmidt, Leah Marie Eskiocak, Banu Kohn, Ryan Dang, Celeste Joshi, Nikhil DuPage, Michel J. Lee, Da-Yae Jacks, Tyler E |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Schmidt, Leah Marie Eskiocak, Banu Kohn, Ryan Dang, Celeste Joshi, Nikhil DuPage, Michel J. Lee, Da-Yae Jacks, Tyler E |
| author_sort | Schmidt, Leah Marie |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T11:41:52Z |
| format | Article |
| id | mit-1721.1/125983 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T11:41:52Z |
| publishDate | 2020 |
| publisher | National Academy of Sciences |
| record_format | dspace |
| spelling | mit-1721.1/1259832022-10-01T05:22:21Z Enhanced adaptive immune responses in lung adenocarcinoma through natural killer cell stimulation Schmidt, Leah Marie Eskiocak, Banu Kohn, Ryan Dang, Celeste Joshi, Nikhil DuPage, Michel J. Lee, Da-Yae Jacks, Tyler E Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT 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. National Institutes of Health (Grant U54 CA126515-01) National Institutes of Health (Grant R01-CA185020-01) 2020-06-25T18:10:33Z 2020-06-25T18:10:33Z 2019-08 2019-03 2019-12-10T18:41:31Z Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 https://hdl.handle.net/1721.1/125983 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 en http://dx.doi.org/10.1073/pnas.1904253116 Proceedings of the National Academy of Sciences 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. application/pdf National Academy of Sciences PNAS |
| spellingShingle | Schmidt, Leah Marie Eskiocak, Banu Kohn, Ryan Dang, Celeste Joshi, Nikhil DuPage, Michel J. Lee, Da-Yae Jacks, Tyler E Enhanced adaptive immune responses in lung adenocarcinoma through natural killer cell stimulation |
| title | Enhanced adaptive immune responses in lung adenocarcinoma through natural killer cell stimulation |
| title_full | Enhanced adaptive immune responses in lung adenocarcinoma through natural killer cell stimulation |
| title_fullStr | Enhanced adaptive immune responses in lung adenocarcinoma through natural killer cell stimulation |
| title_full_unstemmed | Enhanced adaptive immune responses in lung adenocarcinoma through natural killer cell stimulation |
| title_short | Enhanced adaptive immune responses in lung adenocarcinoma through natural killer cell stimulation |
| title_sort | enhanced adaptive immune responses in lung adenocarcinoma through natural killer cell stimulation |
| url | https://hdl.handle.net/1721.1/125983 |
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