| First Author | Mensurado S | Year | 2018 |
| Journal | PLoS Biol | Volume | 16 |
| Issue | 5 | Pages | e2004990 |
| PubMed ID | 29750788 | Mgi Jnum | J:326810 |
| Mgi Id | MGI:6159527 | Doi | 10.1371/journal.pbio.2004990 |
| Citation | Mensurado S, et al. (2018) Tumor-associated neutrophils suppress pro-tumoral IL-17+ gammadelta T cells through induction of oxidative stress. PLoS Biol 16(5):e2004990 |
| abstractText | Interleukin 17 (IL-17)-producing gammadelta T cells (gammadelta17 T cells) have been recently found to promote tumor growth and metastasis formation. How such gammadelta17 T-cell responses may be regulated in the tumor microenvironment remains, however, largely unknown. Here, we report that tumor-associated neutrophils can display an overt antitumor role by strongly suppressing gammadelta17 T cells. Tumor-associated neutrophils inhibited the proliferation of murine CD27- Vgamma6+ gammadelta17 T cells via induction of oxidative stress, thereby preventing them from constituting the major source of pro-tumoral IL-17 in the tumor microenvironment. Mechanistically, we found that low expression of the antioxidant glutathione in CD27- gammadelta17 T cells renders them particularly susceptible to neutrophil-derived reactive oxygen species (ROS). Consistently, superoxide deficiency, or the administration of a glutathione precursor, rescued CD27- Vgamma6+ gammadelta17 T-cell proliferation in vivo. Moreover, human Vdelta1+ gammadelta T cells, which contain most gammadelta17 T cells found in cancer patients, also displayed low glutathione levels and were potently inhibited by ROS. This work thus identifies an unanticipated, immunosuppressive yet antitumoral, neutrophil/ROS/gammadelta17 T-cell axis in the tumor microenvironment. |
