Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Urology, Shunde People's Hospital, Southern Medical University, Guangdong, China.
Cancer Lett. 2017 Oct 10;406:27-35. doi: 10.1016/j.canlet.2017.07.029. Epub 2017 Aug 8.
Program death receptor-1 (PD-1)/program death ligand 1 (PD-L1) signaling plays an important role in tumor adaptive immune resistance. The streptavidin-granulocyte-macrophage colony stimulating factor (SA-GM-CSF) surface-modified tumor cells vaccine developed through our novel protein-anchor technology could significantly promote the activation of dendritic cells. Although GM-CSF vaccine could significantly increase the number of tumor-specific CD8T-cells, the majority of these CD8T-cells expressed PD-1. Moreover, GM-CSF vaccine up-regulated the PD-L1 expression of tumor cells, resulting in immune resistance. Adding PD-1/PD-L1 blockade to GM-CSF vaccine therapy could significantly increase the population of CD4 T, CD8 T and CD8 IFN-γ T but not CD4 Foxp3 T-cells and induced the highest production of IFN-γ. PD-1/PD-L1 blockade could effectively rescue the tumor-specific T lymphocytes generated by the GM-CSF vaccine, resulting in consistent tumor rejection. Taken together, PD-1/PD-L1 blockade combined with SA-GM-CSF-modified vaccine could effectively induce a strong specific antitumor immune response against prostate cancer.
程序性死亡受体 1（PD-1）/程序性死亡配体 1（PD-L1）信号通路在肿瘤适应性免疫抵抗中发挥着重要作用。我们通过新型蛋白锚定技术开发的链霉亲和素-粒细胞-巨噬细胞集落刺激因子（SA-GM-CSF）表面修饰肿瘤细胞疫苗可显著促进树突状细胞的激活。虽然 GM-CSF 疫苗可显著增加肿瘤特异性 CD8T 细胞的数量，但大多数这些 CD8T 细胞表达 PD-1。此外，GM-CSF 疫苗上调了肿瘤细胞的 PD-L1 表达，导致免疫抵抗。将 PD-1/PD-L1 阻断加入 GM-CSF 疫苗治疗中可显著增加 CD4T、CD8T 和 CD8IFN-γT 细胞的数量，但不会增加 CD4Foxp3T 细胞的数量，并诱导最高水平的 IFN-γ产生。PD-1/PD-L1 阻断可有效挽救 GM-CSF 疫苗产生的肿瘤特异性 T 淋巴细胞，从而导致一致的肿瘤排斥。总之，PD-1/PD-L1 阻断联合 SA-GM-CSF 修饰疫苗可有效诱导针对前列腺癌的强烈特异性抗肿瘤免疫反应。
