| First Author | Li W | Year | 2020 |
| Journal | Sci Transl Med | Volume | 12 |
| Issue | 549 | PubMed ID | 32581136 |
| Mgi Jnum | J:297225 | Mgi Id | MGI:6441618 |
| Doi | 10.1126/scitranslmed.aay9013 | Citation | Li W, et al. (2020) cGAS-STING-mediated DNA sensing maintains CD8(+) T cell stemness and promotes antitumor T cell therapy. Sci Transl Med 12(549) |
| abstractText | Although cGAS-STING-mediated DNA sensing in tumor cells or phagocytes is central for launching antitumor immunity, the role of intrinsic cGAS-STING activation in T cells remains unknown. Here, we observed that peripheral blood CD8(+) T cells from patients with cancer showed remarkably compromised expression of the cGAS-STING cascade. We demonstrated that the cGAS-STING cascade in adoptively transferred CD8(+) T cells was essential for antitumor immune responses in the context of T cell therapy in mice. Mechanistically, cell-autonomous cGAS and STING promoted the maintenance of stem cell-like CD8(+) T cells, in part, by regulating the transcription factor TCF1 expression. Moreover, autocrine cGAS-STING-mediated type I interferon signaling augmented stem cell-like CD8(+) T cell differentiation program mainly by restraining Akt activity. In addition, genomic DNA was selectively enriched in the cytosol of mouse CD8(+) T cells upon in vitro and in vivo stimulation. STING agonism enhanced the formation of stem-like central memory CD8(+) T cells from patients with cancer and potentiated antitumor responses of CAR-T cell therapy in a xenograft model. These findings advance our understanding of inherent cGAS-STING activation in T cells and provide insight into the development of improved T cell therapy by harnessing the cGAS-STING pathway for cancer immunotherapy. |
