%0 Journal Article
%T Magnitude of Therapeutic STING Activation Determines CD8+ T Cell-Mediated Anti-tumor Immunity.
%A Sivick KE
%A Desbien AL
%A Glickman LH
%A Reiner GL
%A Corrales L
%A Surh NH
%A Hudson TE
%A Vu UT
%A Francica BJ
%A Banda T
%A Katibah GE
%A Kanne DB
%A Leong JJ
%A Metchette K
%A Bruml JR
%A Ndubaku CO
%A McKenna JM
%A Feng Y
%A Zheng L
%A Bender SL
%A Cho CY
%A Leong ML
%A van Elsas A
%A Dubensky TW
%A McWhirter SM
%J Cell Rep
%V 25
%N 11
%D 12 2018 11
%M 30540940
暂无%R 10.1016/j.celrep.2018.11.047
%X 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.