肿瘤细胞治疗研究
英文原题：Targeting the androgen receptor to enhance NK cell killing efficacy in bladder cancer by modulating ADAR2/circ_0001005/PD-L1 signaling.
这些结果表明，靶向新发现的 ADAR2/circ_0001005/miR-200a-3p/PD-L1 通路以影响抗肿瘤免疫，可能抑制 BCa 的进展并提高免疫治疗疗效。
尽管雄激素受体（AR）可影响膀胱癌（BCa）的发生和进展，但其对肿瘤免疫逃逸的影响仍不清楚。在此，我们发现靶向AR可通过降低PD-L1表达来增强自然杀伤（NK）细胞的杀肿瘤效力。抗雄激素治疗和AR敲低均通过下调circ_0001005有效降低膜PD-L1表达，从而促进NK细胞介导的BCa细胞杀伤。在机制上，AR通过RNA编辑基因ADAR2上调circRNA circ_0001005的表达。circ_0001005竞争性海绵吸附miRNA miR-200a-3p以促进PD-L1表达。临床前BCa异种移植小鼠模型进一步使用小分子circ_0001005-shRNA证实了这一新发现的信号通路可改善NK细胞对BCa肿瘤细胞的杀伤。总之，这些结果表明，靶向新发现的ADAR2/circ_0001005/miR-200a-3p/PD-L1通路以影响抗肿瘤免疫，可能抑制BCa进展并提高免疫治疗疗效。
Although androgen receptor (AR) can influence bladder cancer (BCa) initiation and progression, its impact on tumor immune escape remains unclear. Here, we found that targeting AR could enhance natural killer (NK) cell tumor-killing efficacy by decreasing PD-L1 expression. Both antiandrogen treatment and AR knockdown effectively reduced membrane PD-LI expression to facilitate NK cell-mediated BCa cell killing by downregulating circ_0001005. Mechanistically, AR upregulated circRNA circ_0001005 expression via the RNA-editing gene ADAR2. circ_0001005 competitively sponged the miRNA miR-200a-3p to promote PD-L1 expression. A preclinical BCa xenograft mouse model further confirmed this newly identified signaling using the small molecule circ_0001005-shRNA to improve NK cell killing of BCa tumor cells. Collectively, these results suggest that targeting the newly identified ADAR2/circ_0001005/miR-200a-3p/PD-L1 pathway to impact antitumor immunity may suppress progression and boost immunotherapeutic efficacy in BCa.
MEMBER ACCOUNT
登录成功会直接打开下一页。
