Kang Tae Heung, Kim Young Seob, Kim Seokho, Yang Benjamin, Lee Je-Jung, Lee Hyun-Ju, Lee Jaemin, Jung In Duk, Han Hee Dong, Lee Seung-Hyun, Koh Sang Seok, Wu T-C, Park Yeong-Min
Department of Immunology, KU Open Innovation Center, School of Medicine, Konkuk University, Chungju, South Korea.
Aging Research Institute, Korea Research Institute of Bioscience & Biotechnology, Daejeon, South Korea.
Oncotarget. 2015 Sep 29;6(29):27751-62. doi: 10.18632/oncotarget.4859.
Dendritic cell (DC) based cancer vaccines represent a promising immunotherapeutic strategy against cancer. To enhance the modest immunogenicity of DC vaccines, various adjuvants are often incorporated. Particularly, most of the common adjuvants are derived from bacteria. In the current study, we evaluate the use of a human pancreatic cancer derived protein, pancreatic adenocarcinoma upregulated factor (PAUF), as a novel DC vaccine adjuvant. We show that PAUF can induce activation and maturation of DCs and activate NFkB by stimulating the Toll-like receptor signaling pathway. Furthermore, vaccination with PAUF treated DCs pulsed with E7 or OVA peptides leads to generation of E7 or OVA-specific CD8+ T cells and memory T cells, which correlate with long term tumor protection and antitumor effects against TC-1 and EG.7 tumors in mice. Finally, we demonstrated that PAUF mediated DC activation and immune stimulation are dependent on TLR4. Our data provides evidence supporting PAUF as a promising adjuvant for DC based therapies, which can be applied in conjunction with other cancer therapies. Most importantly, our results serve as a reference for future investigation of human based adjuvants.
基于树突状细胞（DC）的癌症疫苗是一种很有前景的癌症免疫治疗策略。为提高DC疫苗适度的免疫原性，常加入各种佐剂。特别是，大多数常见佐剂都来源于细菌。在本研究中，我们评估了一种源自人胰腺癌的蛋白质——胰腺癌上调因子（PAUF）作为新型DC疫苗佐剂的用途。我们发现PAUF可诱导DC的激活和成熟，并通过刺激Toll样受体信号通路激活NFkB。此外，用PAUF处理并用E7或OVA肽脉冲的DC进行疫苗接种可导致产生E7或OVA特异性CD8 + T细胞和记忆T细胞，这与小鼠对TC-1和EG.7肿瘤的长期肿瘤保护和抗肿瘤作用相关。最后，我们证明PAUF介导的DC激活和免疫刺激依赖于TLR4。我们的数据为支持PAUF作为基于DC疗法的有前景佐剂提供了证据，该佐剂可与其他癌症疗法联合应用。最重要的是，我们的结果为未来基于人类的佐剂研究提供了参考。
