| First Author | Shen W | Year | 2023 |
| Journal | Cancer Sci | Volume | 114 |
| Issue | 5 | Pages | 1816-1829 |
| PubMed ID | 36715504 | Mgi Jnum | J:337866 |
| Mgi Id | MGI:7506707 | Doi | 10.1111/cas.15738 |
| Citation | Shen W, et al. (2023) IFN-gamma-STAT1-mediated NK2R expression is involved in the induction of antitumor effector CD8(+) T cells in vivo. Cancer Sci 114(5):1816-1829 |
| abstractText | The induction of antitumor effector T cells in the tumor microenvironment is a crucial event for cancer immunotherapy. Neurokinin receptor 2 (NK2R), a G protein-coupled receptor for neurokinin A (NKA), regulates diverse physiological functions. However, the precise role of NKA-NK2R signaling in antitumor immunity is unclear. Here, we found that an IFN-gamma-STAT1 cascade augmented NK2R expression in CD8(+) T cells, and NK2R-mediated NKA signaling was involved in inducing antitumor effector T cells in vivo. The administration of a synthetic analog of double-stranded RNA, polyinosinic-polycytidylic acid (poly I:C), into a liver cancer mouse model induced type I and type II IFNs and significantly suppressed the tumorigenesis of Hepa1-6 liver cancer cells in a STAT1-dependent manner. The reduction in tumor growth was diminished by the depletion of CD8(+) T cells. IFN-gamma stimulation significantly induced NK2R and tachykinin precursor 1 (encodes NKA) gene expression in CD8(+) T cells. NKA stimulation combined with anti-CD3 monoclonal antibody (mAb) treatment significantly augmented IFN-gamma and granzyme B production by CD8(+) T cells compared with the anti-CD3 mAb alone in vitro. ERK1/2 phosphorylation and IkappaBalpha degradation in activated CD8(+) T cells were suppressed under NK2R deficiency. Finally, we confirmed that tumor growth was significantly increased in NK2R-deficient mice compared with that in wild-type mice, and the antitumor effects of poly I:C were abolished by NK2R absence. These findings suggest that IFN-gamma-STAT1-mediated NK2R expression is involved in the induction of antitumor effector T cells in the tumor microenvironment, which contributes to the suppression of cancer cell tumorigenesis in vivo. In this study, we revealed that IFN-gamma-STAT1-mediated NK2R expression is involved in the induction of antitumor effector CD8(+) T cells in the tumor microenvironment, which contributes to suppressing the tumorigenesis of liver cancer cells in vivo. |
