| Intrinsic RIG-I restrains STAT5 activation to modulate antitumor activity of CD8+T cells |
| Author |
Jiang, XY; Lin, J; Shangguan, CF; Wang, XY; Xiang, B; Chen, J; Guo, HZ; Zhang, W; Zhang, J; Shi, Y; Zhu, J; Yang, H |
| Journal |
JOURNAL OF CLINICAL INVESTIGATION |
| Pub Year |
2023 |
| Type |
Article |
| Abstract |
Antitumor activity of CD8+ T cells is potentially restrained by a variety of negative regulatory pathways that are triggered in the tumor microenvironment, yet, the exact mechanisms remain incompletely defined. Here, we report that intrinsic RIG-I in CD8+ T cells represents such a factor, as evidenced by observations that the tumor-restricting effect of endogenous or adoptively transferred CD8+ T cells was enhanced by intrinsic Rig-I deficiency or inhibition, with the increased accumulation, survival, and cytotoxicity of tumor-infiltrating CD8+ T cells. Mechanistically, T cell activation-induced RIG-I upregulation restrained STAT5 activation via competitive sequestering of HSP90. In accordance with this, the frequency of RIG-I+ tumor-infiltrating CD8+ T cells in human colon cancer positively correlated with attenuated survival and effector signatures of CD8+ T cells as well as poor prognosis. Collectively, these results implicate RIG-I as a potentially druggable factor for improving CD8+ T cell-based tumor immunotherapy. |
| Issue |
133 |
| Volume |
133 |
| SCI |
15.9 |
