The CHRNΑ5 gene, which encodes the α5-nicotinic acetylcholine receptor (α5-nAChR), is related to lung cancer and nicotine addiction. Smoking is closely related to the immunosuppressive effect of macrophages. CD47, a phagocytosis checkpoint in macrophages, is a therapeutic target in various cancer types. Nevertheless, the relationship between α5-nAChR and CD47 in lung cancer is still unclear. The present study showed that α5-nAChR mediated CD47 expression via STAT3 signaling, consequently leading to tumor progression and immune suppression in lung adenocarcinoma (LUAD). α5-nAChR expression was correlated with STAT3 expression, CD47 expression, smoking status and poor prognosis of LUAD in vivo. In vitro, α5-nAChR expression mediated the phosphorylation of STAT3, and phosphorylated STAT3 bound to the CD47 promoter and mediated CD47 expression. Downregulation of α5-nAChR and/or CD47 significantly reduced cell proliferation, migration, invasion, stemness and IL-10 expression, but increased TNF-α expression and phagocytosis of macrophages in LUAD. Furthermore, α5-nAChR/CD47 signaling contributed to the growth of subcutaneous xenograft tumors and liver metastasis of tumors in mice. Therefore, the α5-nAChR/STAT3/CD47 axis contributed to the progression and immune escape of lung cancer and may be a potential target for LUAD immunotherapy.

中文翻译：

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α5-nAChR/STAT3/CD47 轴有助于尼古丁相关的肺腺癌进展和免疫逃逸。

CHRNAA5基因编码α5-烟碱乙酰胆碱受体(α5-nAChR)，与肺癌和尼古丁成瘾有关。吸烟与巨噬细胞的免疫抑制作用密切相关。CD47 是巨噬细胞中的吞噬检查点，是多种癌症类型的治疗靶点。然而，α5-nAChR与CD47在肺癌中的关系仍不清楚。本研究表明，α5-nAChR 通过 STAT3 信号传导介导 CD47 表达，从而导致肺腺癌 (LUAD) 的肿瘤进展和免疫抑制。α5-nAChR表达与体内STAT3表达、CD47表达、吸烟状况及LUAD不良预后相关。在体外，α5-nAChR的表达介导STAT3的磷酸化，磷酸化的STAT3与CD47启动子结合并介导CD47的表达。α5-nAChR和/或CD47的下调显着降低了LUAD中的细胞增殖、迁移、侵袭、干性和IL-10表达，但增加了TNF-α表达和巨噬细胞的吞噬作用。此外，α5-nAChR/CD47信号传导有助于小鼠皮下异种移植肿瘤的生长和肿瘤的肝转移。因此，α5-nAChR/STAT3/CD47轴有助于肺癌的进展和免疫逃逸，可能是LUAD免疫治疗的潜在靶点。