先天性巨痣GCMN为一种良性增殖肿瘤，尚无有效治疗方法。针对肿瘤免疫逃逸，靶向阻断免疫检查点，解除免疫逃逸，可使淋巴细胞杀死肿瘤细胞。而程序性死亡受体PD-1及配体PD-L1是最具应用前景的免疫检查点，已在多种肿瘤中（特别是黑色素瘤）取得进展。GCMN同黑色素瘤具有同源性，理论上具有免疫相似性。预实验中晕痣标本研究提示，机体能产生针对黑痣细胞的特异性免疫。巨痣标本研究显示，GCMN中痣细胞表达PD-L1，提示存在PD-1/PD-L1介导的免疫耐受。另外文献表明，干扰素-γ（IFN-γ）可提高PD-1/PD-L1阻断剂免疫治疗效果。据上述研究提出假设，使用抗PD-1/PD-L1阻断剂，可激活免疫系统杀伤GCMN细胞。联合使用IFN-γ可增加抗PD-1/PD-L1疗效。本实验拟通过体外淋巴细胞共培养体系，及动物在体试验，验证PD-1/PD-L1阻断剂联合应用IFN-γ对GCMN的免疫治疗作用。

Giant congenital melanocytic nevus (GCMN) is a benign proliferation tumor, there is no effective treatment now. In order to prevent tumor cell immune escape, targeted intervention can activate lymphocyte to attack tumor cells. Program death receptor-1 (PD-1) and its ligand PD-L1 is the most promising immunological checkpoint, which has been proved effective in many malignant tumors, especially melanoma. Theoretically, GCMN homology with melanoma and has similar tumor immunity. Our preliminary results on halo nevus specimens suggest that the body trigger a specific immune response against nevus cells. GCMN specimens found that PD-L1 was expressed in nevus cells, suggesting that there has a PD-1/PD-L1-mediated immune tolerance. Additional literature suggests that Interferon-γ (IFN-γ) enhances the immunotherapeutic effect of PD-1/PD-L1 blockers. According to the above study, we hypothesized that anti-PD-1/PD-L1 blockers can activate the immune system to attack GCMN cells. Combination of IFN-γ can enhance anti-PD-1/PD-L1 efficacy. In this project, we verify the immunotherapeutic effect of PD-1/PD-L1 blocker combined with IFN-γ on GCMN by in vitro lymphocyte co-culture system and in vivo experiments in animals.