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Open AccessArticle

Blockade of PD-L1 Enhances Cancer Immunotherapy by Regulating Dendritic Cell Maturation and Macrophage Polarization

1
Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei 100, Taiwan
2
Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei 100, Taiwan
3
Department of Obstetrics and Gynecology, Far Eastern Memorial Hospital, New Taipei 220, Taiwan
4
Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan
5
Department of Obstetrics and Gynecology, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu City 300, Taiwan
6
Department of Anesthesiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(9), 1400; https://doi.org/10.3390/cancers11091400
Received: 9 August 2019 / Revised: 6 September 2019 / Accepted: 16 September 2019 / Published: 19 September 2019
The immuno-inhibitory checkpoint PD-L1, regulated by tumor cells and antigen-presenting cells (APCs), dampened the activation of T cells from the PD-1/PD-L1 axis. PD-L1-expressing APCs rather than tumor cells demonstrated the essential anti-tumor effects of anti-PD-L1 monotherapy in preclinical tumor models. Using the murine tumor model, we investigated whether anti-PD-L1 antibody increased the antigen-specific immune response and anti-tumor effects induced by the antigen-specific protein vaccine, as well as the possible mechanisms regarding activation of APCs. Anti-PD-L1 antibody combined with the PEK protein vaccine generated more potent E7-specific immunity (including the number and cytotoxic activity of E7-specific cytotoxic CD8+ T lymphocytes) and anti-tumor effects than protein vaccine alone. Anti-PD-L1 antibody enhanced the maturation of dendritic cells and the proportion of M1-like macrophages in tumor-draining lymph nodes and tumors in tumor-bearing mice treated with combinatorial therapy. PD-L1 blockade overturned the immunosuppressive status of the tumor microenvironment and then enhanced the E7 tumor-specific antigen-specific immunity and anti-tumor effects generated by an E7-specific protein vaccine through modulation of APCs in an E7-expressing small tumor model. Tumor-specific antigen (like HPV E7 antigen)-specific immunotherapy combined with APC-targeting modality by PD-L1 blockade has a high translational potential in E7-specific cancer therapy. View Full-Text
Keywords: antigen-specific protein vaccine; anti-PD-L1 antibody; antigen-presenting cells; dendritic cells; macrophages antigen-specific protein vaccine; anti-PD-L1 antibody; antigen-presenting cells; dendritic cells; macrophages
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MDPI and ACS Style

Sun, N.-Y.; Chen, Y.-L.; Wu, W.-Y.; Lin, H.-W.; Chiang, Y.-C.; Chang, C.-F.; Tai, Y.-J.; Hsu, H.-C.; Chen, C.-A.; Sun, W.-Z.; Cheng, W.-F. Blockade of PD-L1 Enhances Cancer Immunotherapy by Regulating Dendritic Cell Maturation and Macrophage Polarization. Cancers 2019, 11, 1400.

AMA Style

Sun N-Y, Chen Y-L, Wu W-Y, Lin H-W, Chiang Y-C, Chang C-F, Tai Y-J, Hsu H-C, Chen C-A, Sun W-Z, Cheng W-F. Blockade of PD-L1 Enhances Cancer Immunotherapy by Regulating Dendritic Cell Maturation and Macrophage Polarization. Cancers. 2019; 11(9):1400.

Chicago/Turabian Style

Sun, Nai-Yun; Chen, Yu-Li; Wu, Wen-Yih; Lin, Han-Wei; Chiang, Ying-Cheng; Chang, Chi-Fang; Tai, Yi-Jou; Hsu, Heng-Cheng; Chen, Chi-An; Sun, Wei-Zen; Cheng, Wen-Fang. 2019. "Blockade of PD-L1 Enhances Cancer Immunotherapy by Regulating Dendritic Cell Maturation and Macrophage Polarization" Cancers 11, no. 9: 1400.

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