| First Author | Sivick KE | Year | 2018 |
| Journal | Cell Rep | Volume | 25 |
| Issue | 11 | Pages | 3074-3085.e5 |
| PubMed ID | 30540940 | Mgi Jnum | J:270776 |
| Mgi Id | MGI:6278708 | Doi | 10.1016/j.celrep.2018.11.047 |
| Citation | Sivick KE, et al. (2018) Magnitude of Therapeutic STING Activation Determines CD8(+) T Cell-Mediated Anti-tumor Immunity. Cell Rep 25(11):3074-3085.e5 |
| abstractText | Intratumoral (IT) STING activation results in tumor regression in preclinical models, yet factors dictating the balance between innate and adaptive anti-tumor immunity are unclear. Here, clinical candidate STING agonist ADU-S100 (S100) is used in an IT dosing regimen optimized for adaptive immunity to uncover requirements for a T cell-driven response compatible with checkpoint inhibitors (CPIs). In contrast to high-dose tumor ablative regimens that result in systemic S100 distribution, low-dose immunogenic regimens induce local activation of tumor-specific CD8(+) effector T cells that are responsible for durable anti-tumor immunity and can be enhanced with CPIs. Both hematopoietic cell STING expression and signaling through IFNAR are required for tumor-specific T cell activation, and in the context of optimized T cell responses, TNFalpha is dispensable for tumor control. In a poorly immunogenic model, S100 combined with CPIs generates a survival benefit and durable protection. These results provide fundamental mechanistic insights into STING-induced anti-tumor immunity. |
