Abstract 1686: Host intrinsic STING is a promising biomarkerfor predicting clinical efficacy of anti-PD-1 inhibitors in lung cancer

Abstract

Abstract Background: The stimulator of IFN genes (STING) signaling pathway plays an important role in anti-tumor immune responses. However, the mechanistic contribution of host and tumor STING signaling to the therapeutic efficacy of anti-PD-1 inhibitors in lung cancer remains unknown. Methods: We analyzed the association of STING with immune makers in TCGA datasets; we evaluated the efficacy of anti-PD-1 inhibitors by coculturing spleen cells with LLC cells in vitro, and inoculating wild type/STING knockdown LLC cells into the flank of wild-type/STING knockout mice in vivo. Furthermore, we measured the expression of STING by multiple immunohistochemistry and immunohistochemistry in lung cancer patients, and analyzed the relationship between expression level of STING in different cells and treatment efficacy of DCB(Durable clinical benefit : CR or PR or SD lasting longer than 6 months) and NDB(No durable clinical benefit : PD or SD that lasted ≤ 6 months) patients receiving immunotherapy. Results: Here we first demonstrated that STING signaling pathway activation was associated with better immunotherapy efficacy in lung cancer patients. Next, we identified two distinct STING expression pattern and found that STING in host cells not in tumor cells was positively correlated with infiltration of CD8+ T cells. More importantly, we demonstrated a loss of therapeutic efficacy of anti-PD-1 inhibitor in STING KO spleen cells and STING KO mice. In contrast, knock down of STING expression in tumor cells had no effect. Furthermore, expression of STING on host cells not in tumor cells was correlated with the efficacy of Anti-PD-1 inhibitors in lung cancer patients. Conclusion: Together, these findings demonstrate that STING expressed in host cells, rather than on tumor cells, plays an essential role in anti-PD-1 inhibitor therapy, suggesting that host intrinsic STING could be predictive of sensitivity to anti-PD-1 inhibitors. Citation Format: Li Zhou, Qiuli Xu, Litang Huang, Ping Zhan, mingxiang ye, Tangfeng Lv, Yong Song. Host intrinsic STING is a promising biomarkerfor predicting clinical efficacy of anti-PD-1 inhibitors in lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1686.