携载STAT6 siRNA超声纳米泡靶向阻抑JAK/STAT6通路对M2极化与NSCLC免疫治疗研究

肿瘤细胞的浸润和转移与免疫细胞M2型肿瘤相关巨噬细胞（TAM）的极化密切相关。肿瘤细胞分泌IL-4和IL-13激活JAK/STAT6信号通路调控TAM向M2型极化（M2极化），进而上调VEGF、MMPs、IL-10等因子表达、抑制T细胞介导的抗肿瘤细胞免疫应答，致肿瘤细胞浸润转移。M2极化与非小细胞肺癌（NSCLC）的免疫逃逸浸润转移密切相关，JAK/STAT6通路是调控M2极化的关键因素。特异性阻抑STAT6、抑制M2极化、进而增强T细胞介导的免疫应答、抑制肿瘤浸润转移是提高肿瘤免疫治疗关键。基于超声介导纳米泡技术的靶向控释优势和基因沉默高效性，针对M2型TAM对肿瘤抗免疫应答反应，拟设计携载STAT6 siRNA超声纳米泡特异性靶向阻抑JAK/STAT6通路、抑制M2极化，增强T细胞活性，提高NSCLC靶向免疫治疗效果，为研究NSCLC免疫治疗、开发新的靶向药物提供理论依据及新的思路。

Infiltration and metastasis of tumor cells are closely related to the M2 type immune cell from the polarization of tumor-associated macrophages (TAM). Tumor cells activate the JAK/STAT6 signal pathway by secreting IL-4 and IL-13 to regulate the polarization of TAM to M2（M2 polarization）, thereby up-regulating the expression of VEGF, MMPs, IL-10 and other factors, inhibiting T cell-mediated anti-tumor cellular immune responses, and inducing tumor cell infiltration and metastasis. M2 polarization is closely related to immune escape, infiltration and metastasis of non-small cell lung cancer (NSCLC), and JAK/STAT6 pathway is a key factor regulating M2 polarization. The key to improve tumor immunotherapy are specific inhibition of STAT6, inhibition of M2 polarization, and thus inprovement of T cell-mediated immune response and then inhibition of tumor infiltration and metastasis. Based on the targeted controlled release advantage and gene silencing efficiency of ultrasound-mediated nanobubbles technology, with the aim of the anti-immune response of M2 type TAM to tumors, we plan to design ultrasonic nanobubbles with STAT6 siRNA, which specifically target the inhibition of JAK/STAT6 pathway, thereby inhibiting the M2 polarization , and then enhancing of the activity of T cells, improving the therapeutic effect of NSCLC-targeted immunotherapy, with the purpose of providing theoretical basis and new ideas for NSCLC immunotherapy and developing new targeted drugs.