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Cell Rep. 2018 Dec 11;25(11):3074-3085.e5. doi: 10.1016/j.celrep.2018.11.047.

Magnitude of Therapeutic STING Activation Determines CD8+ T Cell-Mediated Anti-tumor Immunity.

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Aduro Biotech, Inc., Berkeley, CA 94710, USA.
Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA.
Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA.
Aduro Biotech, Inc., Berkeley, CA 94710, USA. Electronic address:


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, TNFα 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.


ADU-S100; CD8(+) T cell; ImmunoOncology; STING; abscopal immunity; anti-tumor immunity; checkpoint inhibitor; cyclic dinucleotide; intratumoral; type I interferon

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