[摘 要] 目的：探究晚期黏膜黑色素瘤患者免疫联合抗血管生成治疗前后外周血淋巴细胞免疫分型、细胞因子水平与治疗效 果及患者预后的相关性。方法：纳入分析2019年4月至2022年6月在南京大学医学院附属鼓楼医院收治的28例晚期黏膜黑色 素瘤患者，所有患者均接受卡瑞利珠单抗（PD-1抑制剂）及甲磺酸阿帕替尼（抗血管生成药物）的联合治疗，采集治疗前和2周 期治疗后患者外周血，进行淋巴细胞免疫分型、细胞因子水平检测，评估其与治疗效果及患者预后的相关性。结果：黏膜黑色素 瘤患者接受卡瑞利珠单抗联合甲磺酸阿帕替尼治疗2周期后，外周血PD-1阳性细胞毒性T淋巴细胞（CD3+ CD8+ CD279+ 细胞）比 例显著降低（P < 0.001），治疗响应的患者NK细胞（CD3- CD16+ CD56+ 细胞）比例明显升高（P = 0.005 4）。治疗前外周血IFN-γ水 平与总生存期（OS）相关（P = 0.013），IFN-γ低水平的患者中位OS为329天，高水平的患者中位OS未达到。基线IFN-γ水平越高， PFS倾向获益越大。结论：外周血PD-1阳性T淋巴细胞、NK细胞比例、IFN-γ水平对接受免疫联合抗血管生成治疗的晚期黏膜 黑色素瘤患者的疗效及预后可能有预测价值，未来仍需要大样本研究以更好地表征临床应用潜力。

[Abstract] Objective: To investigate the correlation between peripheral blood lymphocyte immunophenotyping, cytokine levels before and after immune and anti-angiogenesis combined therapy, and treatment efficacy as well as prognosis in patients with advanced mucosal melanoma. Methods: A total of 28 patients with advanced mucosal melanoma admitted to the Drum Tower Hospital of Nanjing University School of Medicine from April 2019 to June 2022 were included in this analysis. All patients received combined treatment of camrelizumab (PD-1 inhibitor) and apatinib (anti-angiogenic drug). Peripheral blood samples were collected before treatment and after two cycles of treatment for lymphocyte immunophenotyping and cytokine level testing. The correlation between these immune markers and treatment efficacy as well as patient prognosis was evaluated. Results: After two cycles of treatment with camrelizumab and apatinib in patients with mucosal melanoma, the proportion of PD-1 positive cytotoxic T lymphocytes (CD3+ CD8+ CD279+ cells) in peripheral blood was significantly reduced (P < 0.001), while the proportion of NK cells (CD3- CD16+ CD56+ cells) was significantly increased (P = 0.0054). Pre-treatment peripheral blood IFN- γ levels were found to be associated with overall survival (OS) (P = 0.013). Patients with low IFN-γ levels had a median OS of 329 days, while the median OS for patients with high IFN-γ levels was not reached. Higher baseline IFN-γ levels were associated with a greater benefit in progressionfree survival (PFS). Conclusion: The proportion of PD-1-positive T lymphocytes, NK cells and IFN-γ levels in peripheral blood may have predictive value for the efficacy and prognosis of advanced mucosal melanoma patients undergoing immunotherapy and antiangiogenesis combined therapy. Future large-sample studies are needed to better characterize the clinical potential of these markers.

国家自然科学基金（No.82073365，No.81872484）；江苏省社会发展基金（No.BE2019605）