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Supplementary Table S1 from Mitigating SOX2-potentiated Immune Escape of Head and Neck Squamous Cell Carcinoma with a STING-inducing Nanosatellite Vaccine
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posted on 2023-03-31, 19:51 authored by Yee Sun Tan, Kanokwan Sansanaphongpricha, Yuying Xie, Christopher R. Donnelly, Xiaobo Luo, Blake R. Heath, Xinyi Zhao, Emily Bellile, Hongxiang Hu, Hongwei Chen, Peter J. Polverini, Qianming Chen, Simon Young, Thomas E. Carey, Jacques E. Nör, Robert L. Ferris, Gregory T. Wolf, Duxin Sun, Yu L. LeiList of deferentially expressed genes in HNSCC cancer cells resistant to immune killing
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NIH
Mcubed
Rogel Cancer Center
POM Clinical Research
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ARTICLE ABSTRACT
Purpose: The response rates of Head and Neck Squamous Cell Carcinoma (HNSCC) to checkpoint blockade are below 20%. We aim to develop a mechanism-based vaccine to prevent HNSCC immune escape.Experimental Design: We performed RNA-Seq of sensitive and resistant HNSCC cells to discover central pathways promoting resistance to immune killing. Using biochemistry, animal models, HNSCC microarray, and immune cell deconvolution, we assessed the role of SOX2 in inhibiting STING-type I interferon (IFN-I) signaling-mediated antitumor immunity. To bypass SOX2-potentiated STING suppression, we engineered a novel tumor antigen–targeted nanosatellite vehicle to enhance the efficacy of STING agonist and sensitize SOX2-expressing HNSCC to checkpoint blockade.Results: The DNA-sensing defense response is the most suppressed pathway in immune-resistant HNSCC cells. We identified SOX2 as a novel inhibitor of STING. SOX2 facilitates autophagy-dependent degradation of STING and inhibits IFN-I signaling. SOX2 potentiates an immunosuppressive microenvironment and promotes HNSCC growth in vivo in an IFN-I-dependent fashion. Our unique nanosatellite vehicle significantly enhances the efficacy of STING agonist. We show that the E6/E7–targeted nanosatellite vaccine expands the tumor-specific CD8+ T cells by over 12-fold in the tumor microenvironment and reduces tumor burden. A combination of nanosatellite vaccine with anti-PD-L1 significantly expands tumor-specific CTLs and limits the populations expressing markers for exhaustion, resulting in more effective tumor control and improved survival.Conclusions: SOX2 dampens the immunogenicity of HNSCC by targeting the STING pathway for degradation. The nanosatellite vaccine offers a novel and effective approach to enhance the adjuvant potential of STING agonist and break cancer tolerance to immunotherapy. Clin Cancer Res; 24(17); 4242–55. ©2018 AACR.Usage metrics
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