Poly(I:C) enhanced anti-cervical cancer immunities induced by dendritic cells-derived exosomes

被引:64
作者
Chen, Shisheng [1 ,2 ]
Lv, Mingfen [3 ]
Fang, Shan [1 ,2 ]
Ye, Wenxia [1 ,2 ]
Gao, Yu [1 ,2 ]
Xu, Yunsheng [3 ]
机构
[1] Wenzhou Med Univ, Dept Dermatol, Affiliated Hosp 2, 109 Xueyuan Western Rd, Wenzhou 325027, Zhejiang, Peoples R China
[2] Wenzhou Med Univ, Yuying Childrens Hosp, 109 Xueyuan Western Rd, Wenzhou 325027, Zhejiang, Peoples R China
[3] Wenzhou Med Univ, Affiliated Hosp 1, Dept Dermatovenereol, South Baixiang Rd, Wenzhou 325000, Zhejiang, Peoples R China
基金
中国国家自然科学基金;
关键词
Cervical cancer; Poly(I:C); Dendritic cells; Immunity responses; ANTITUMOR IMMUNE-RESPONSE; IN-VIVO; IMMUNOTHERAPY; ADJUVANTS; VACCINES; IMMUNIZATION; PROTEIN; OVARIAN; FUTURE;
D O I
10.1016/j.ijbiomac.2018.02.034
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Dendritic cell (DC)-derived exosomes (Dexo) has been confirmed to be able to induce the specific anti-tumor immune response ex vivo and in vivo. Here, the aim of this study was to evaluate the application of the antigen pulsed Dexo as a new vaccination platform in immunotherapy for cervical cancer. The immunogenic profile of the different Dexo was assessed by the cell proliferation, cytokines secretion and effector functions of CD8(+) T cells and the splenocytes from Dexo-vaccinated mice. Furthermore, the anti-tumor immunity elicited by Dexo was further compared in cervical cancer-bearing mice. Dexo from DCs loaded with E7(49-57) peptide could efficiently induce the cytotoxic activity of CD8(+) T cells on TC-1 tumor cells ex vivo, the proliferation and IFN-gamma, excretion of CD8(+) T cells. Moreover, Dexo vaccine promoted the immune responses of vaccinated mice splenocytes induced by antigen E7 in vitro restimulation. Of note, poly(I:C) was significantly more potent inducer of the antigen-loaded Dexo mediated protective immunity responses for cervical cancer and further evidenced by that Dexo(E7 + pIC) markedly inhibited the tumor growth and improved the survival rate of the tumor-bearing mice. We provided evidence that poly(I:C) dramatically increased the potent antitumoral immunity induced by antigen-pulsed Dexo for ameliorating cervical cancer. (C) 2018 Published by Elsevier B.V.
引用
收藏
页码:1182 / 1187
页数:6
相关论文
共 35 条
[1]   The rationale for combined chemo/immunotherapy using a Toll-like receptor 3 (TLR3) agonist and tumour-derived exosomes in advanced ovarian cancer [J].
Adams, A ;
Navabi, H ;
Croston, D ;
Coleman, S ;
Tabi, Z ;
Clayton, A ;
Jasani, B ;
Mason, MD .
VACCINE, 2005, 23 (17-18) :2374-2378
[2]   Exosomes from Dendritic Cells Loaded with Chaperone-Rich Cell Lysates Elicit a Potent T Cell Immune Response Against Intracranial Glioma in Mice [J].
Bu, Ning ;
Wu, Haiqin ;
Zhang, Guilian ;
Zhan, Shuqin ;
Zhang, Ru ;
Sun, Hong ;
Du, Yun ;
Yao, Li ;
Wang, Huqing .
JOURNAL OF MOLECULAR NEUROSCIENCE, 2015, 56 (03) :631-643
[3]   Dendritic cell derived-exosomes:: biology and clinical implementations [J].
Chaput, Nathalie ;
Flament, Caroline ;
Viaud, Sophie ;
Taieb, Julien ;
Roux, Stephan ;
Spatz, Alain ;
Andre, Fabrice ;
LePecq, Jean-Bernard ;
Boussac, Muriel ;
Garin, Jerome ;
Amigorena, Sebastian ;
Thery, Clotilde ;
Zitvogel, Laurence .
JOURNAL OF LEUKOCYTE BIOLOGY, 2006, 80 (03) :471-478
[4]   Enhanced anti-tumor effects of HPV16E749-57-based vaccine by combined immunization with poly(I:C) and oxygen-regulated protein 150 [J].
Chen, Shisheng ;
Ou, Rongying ;
Tang, Jun ;
Deng, Xiufang ;
Wu, Yuzhang ;
van Velkinburgh, Jennifer C. ;
Ni, Bing ;
Xu, Yunsheng .
CANCER EPIDEMIOLOGY, 2013, 37 (02) :172-178
[5]   Human innate responses and adjuvant activity of TLR ligands in vivo in mice reconstituted with a human immune system [J].
Cheng, Liang ;
Zhang, Zheng ;
Li, Guangming ;
Li, Feng ;
Wang, Li ;
Zhang, Liguo ;
Zurawski, Sandra M. ;
Zurawski, Gerard ;
Levy, Yves ;
Su, Lishan .
VACCINE, 2017, 35 (45) :6143-6153
[6]   Use of adjuvants for immunotherapy [J].
Circelli, Luisa ;
Tornesello, Marialina ;
Buonaguro, Franco M. ;
Buonaguro, Luigi .
HUMAN VACCINES & IMMUNOTHERAPEUTICS, 2017, 13 (08) :1774-1777
[7]   Dendritic cell-based immunotherapy: a basic review and recent advances [J].
Constantino, Joao ;
Gomes, Celia ;
Falcao, Amilcar ;
Neves, Bruno Miguel ;
Cruz, Maria Teresa .
IMMUNOLOGIC RESEARCH, 2017, 65 (04) :798-810
[8]   Synthetic double-stranded RNA poly(I:C) as a potent peptide vaccine adjuvant:: therapeutic activity against human cervical cancer in a rodent model [J].
Cui, Zhengrong ;
Qiu, Fu .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 2006, 55 (10) :1267-1279
[9]   TLR-3 stimulation improves anti-tumor immunity elicited by dendritic cell exosome-based vaccines in a murine model of melanoma [J].
Damo, Martina ;
Wilson, David S. ;
Simeoni, Eleonora ;
Hubbell, Jeffrey A. .
SCIENTIFIC REPORTS, 2015, 5
[10]  
Ghebre RG, 2017, GYNECOL ONCOL REP, V21, P101, DOI 10.1016/j.gore.2017.07.009