| First Author | Schmidt L | Year | 2019 |
| Journal | Proc Natl Acad Sci U S A | Volume | 116 |
| Issue | 35 | Pages | 17460-17469 |
| PubMed ID | 31409707 | Mgi Jnum | J:283605 |
| Mgi Id | MGI:6359004 | Doi | 10.1073/pnas.1904253116 |
| Citation | Schmidt L, et al. (2019) Enhanced adaptive immune responses in lung adenocarcinoma through natural killer cell stimulation. Proc Natl Acad Sci U S A 116(35):17460-17469 |
| abstractText | 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. |
