进展期非小细胞肺癌化疗已达瓶颈期，免疫治疗及微波消融（MWA）应用日益广泛。微波消融具有增强与抑制免疫的双重作用。然而微波消融对程序性死亡受体配体1（PD-L1）影响尚不明确。我们前期研究发现非小细胞肺癌寡转移患者寡转移灶微波消融后原发灶PD-L1表达上调，伴γ干扰素（INF-γ）及CD8+肿瘤浸润淋巴细胞（TIL）增加。微波消融上调PD-L1表达的具体机制尚不明确。本研究旨在NSCLC细胞系、移植瘤模型及大样本NSCLC寡转移患者验证微波消融介导PD-L1表达上调；通过增强或干扰INF-γ联合微波消融确认INFγ在PD-L1表达上调中居于核心地位，通过AKT及STAT3抑制剂联合微波消融明确INF-γ通过PI3K/AKT及JAK-STAT3信号通路介导PD-L1表达；通过免疫抑制剂联合微波消融确认联合治疗可克服PD-L1表达上调所致T细胞免疫抑制。为微波消融联合免疫治疗奠定理论基础。

Chemotherapy for advanced non-small cell lung cancer（NSCLC）has reached the plateau. Immunotherapy and microwave ablation (MWA) have been widely applied in the treatment of NSCLC. MWA has the dual effects of enhancing and inhibiting immunity. However, the effect of microwave ablation on the programmed death receptor ligand-1 (PD-L1) is not yet clear. Our previous study showed the update of PD-L1 expression in primary tumor sites when oligometastatic NSCLC patients treated with MWA for the metastatic tumor sites, accompanied by the update of both gamma interferon (INF-γ) and CD8 + tumor infiltrating lymphocytes (TIL). However, the definite mechanism of microwave ablation to update PD-L1 expression is not yet clear. The aim of this study was to verify that microwave ablation induced the update of PD-L1 expression in NSCLC cell lines, transplanted tumor models and large sample oligometastatic NSCLC patients; Moreover, to demonstrate that INF-γ was the key in the update of PD-L1 expression by enhancing or interfering with INF-γ combined with microwave ablation; to determinate that INF-γ mediates PD-L1 expression through P3K/AKT and JAK-STAT-3 signal pathways by combined AKT and STAT-3 inhibitors with microwave ablation; to verify that immunotherapy plus microwave ablation can overcome T cell immunosuppression induced by elevated PD-L1 expression. The study can provide theoretical basis for microwave ablation combined with immunotherapy.