Abstract：
The stimulator of interferon genes (STING) pathway is important for anticancer immune responses. However, the relative contributions of host and tumour STING in anti-programmed cell death protein 1 (anti-PD-1) inhibitor responses in non-small cell lung cancer (NSCLC) are unknown. STING expression in tumour and blood was associated with anti-PD-1 therapy in NSCLC patients; Moreover, loss of PD-1 inhibitor therapeutic potency was demonstrated in STING KO (knock out) splenocytes and STING KO mice. STING knock-down in tumour cells had no effect. STING on CD8+ T cells and host cells, not tumour cells, correlated with clinical effect of anti-PD-1 therapy in NSCLC patients. Finally, adoptive transfer of CD8+ T cells restored PD-1 inhibitor anticancer effects. STING in host cells but not in tumour cells mediates anti-PD-1 inhibitor responses in cancer immunotherapy and could be used to select advantageous NSCLC patients from immunotherapy.
摘要：
干扰素基因（STING）途径的刺激物对于抗癌免疫应答很重要。然而,宿主和肿瘤STING在非小细胞肺癌(NSCLC)的抗程序性细胞死亡蛋白1(抗PD-1)抑制剂应答中的相对作用尚不清楚.STING在肿瘤和血液中的表达与NSCLC患者的抗PD-1治疗有关；此外，在STINGKO(敲除)脾细胞和STINGKO小鼠中证实了PD-1抑制剂治疗效力的丧失。肿瘤细胞中的STING敲低没有作用。对CD8+T细胞和宿主细胞的STING，不是肿瘤细胞,与NSCLC患者抗PD-1治疗的临床效果相关。最后,CD8+T细胞的过继转移恢复了PD-1抑制剂的抗癌作用。在宿主细胞中而不是在肿瘤细胞中的STING在癌症免疫疗法中介导抗PD-1抑制剂应答,并且可以用于从免疫疗法中选择有利的NSCLC患者。
