Zhang Rui, Tang Lin, Li Qing, Tian Yaomei, Zhao Binyan, Zhou Bailing, Yang Li
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, People's Republic of China.
Mol Biomed. 2021 Dec 5;2(1):37. doi: 10.1186/s43556-021-00058-9.
Dendritic cell (DC)-based cancer vaccines have so far achieved good therapeutic effects in animal experiments and early clinical trials for certain malignant tumors. However, the overall objective response rate in clinical trials rarely exceeds 15%. The poor efficiency of DC migration to lymph nodes (LNs) (< 5%) is one of the main factors limiting the effectiveness of DC vaccines. Therefore, increasing the efficiency of DC migration is expected to further enhance the efficacy of DC vaccines. Here, we used DP7-C (cholesterol modified VQWRIRVAVIRK), which can promote DC migration, as a medium. Through multiomics sequencing and biological experiments, we found that it is the metabolite pantothenic acid (PA) that improves the migration and effectiveness of DC vaccines. We clarified that both DP7-C and PA regulate DC migration by regulating the chemokine receptor CXCR2 and inhibiting miR-142a-3p to affect the NF-κB signaling pathway. This study will lay the foundation for the subsequent use of DP7-C as a universal substance to promote DC migration, further enhance the antitumor effect of DC vaccines, and solve the bottleneck problem of the low migration efficiency and unsatisfactory clinical response rate of DC vaccines.
基于树突状细胞（DC）的癌症疫苗目前在某些恶性肿瘤的动物实验和早期临床试验中已取得良好的治疗效果。然而，临床试验中的总体客观缓解率很少超过15%。DC迁移至淋巴结（LN）的效率低下（<5%）是限制DC疫苗有效性的主要因素之一。因此，提高DC迁移效率有望进一步增强DC疫苗的疗效。在此，我们使用可促进DC迁移的DP7-C（胆固醇修饰的VQWRIRVAVIRK）作为介质。通过多组学测序和生物学实验，我们发现是代谢物泛酸（PA）提高了DC疫苗的迁移和有效性。我们阐明，DP7-C和PA均通过调节趋化因子受体CXCR2并抑制miR-142a-3p来影响NF-κB信号通路，从而调节DC迁移。本研究将为后续将DP7-C用作促进DC迁移的通用物质奠定基础，进一步增强DC疫苗的抗肿瘤作用，并解决DC疫苗迁移效率低和临床缓解率不尽人意的瓶颈问题。
