Magnitude of Therapeutic STING Activation Determines CD8+ T Cell-Mediated Anti-tumor Immunity
Kelsey E. Sivick(Aduro BioTech (United States)), Anthony L. Desbien(Aduro BioTech (United States)), Laura Hix Glickman(Aduro BioTech (United States)), Gabrielle L. Reiner(Aduro BioTech (United States)), Leticia Corrales(Aduro BioTech (United States)), Natalie H. Surh(Aduro BioTech (United States)), Thomas E. Hudson(Aduro BioTech (United States)), Uyen T. Vu(Aduro BioTech (United States)), Brian J. Francica(Aduro BioTech (United States)), Tamara Banda(Aduro BioTech (United States)), George E. Katibah(Aduro BioTech (United States)), David B. Kanne(Aduro BioTech (United States)), Justin J. Leong(Aduro BioTech (United States)), Ken Metchette(Aduro BioTech (United States)), Jacob R. Bruml(Aduro BioTech (United States)), Chudi Ndubaku(Aduro BioTech (United States)), Jeffrey M. McKenna(Novartis (United States)), Feng Yan(Novartis (United States)), Lianxing Zheng(Novartis (United States)), Steven L. Bender(Genomics Institute of the Novartis Research Foundation), Charles Y. Cho(Genomics Institute of the Novartis Research Foundation), Meredith L. Leong(Aduro BioTech (United States)), Andrea van Elsas(Aduro BioTech (United States)), Thomas W. Dubensky(Aduro BioTech (United States)), Sarah M. McWhirter(Aduro BioTech (United States))
Cited by 434Open Access
Abstract
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.
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