TLR7型
免疫系统
癌症免疫疗法
肿瘤微环境
癌症研究
免疫疗法
CD8型
免疫学
重编程
T细胞
免疫抑制
抗原
Toll样受体
生物
医学
先天免疫系统
细胞
生物化学
作者
Sunyoung Kim,Young Ho Kim,Jung‐Eun Kim,Sang‐Nam Lee,Il Woo Shin,Heungsoo Shin,Seung Mo Jin,Young‐Woock Noh,Young Ju Kang,Young Seob Kim,Tae Heung Kang,Yeong‐Min Park,Yong Taik Lim
出处
期刊:ACS Nano
[American Chemical Society]
日期:2019-10-07
卷期号:13 (11): 12671-12686
被引量:93
标识
DOI:10.1021/acsnano.9b04207
摘要
The low therapeutic efficacy of current cancer immunotherapy is related to nonimmunogenic and immunosuppressive tumor microenvironments (TMEs). To overcome these limitations, both the immune priming of antitumoral lymphocytes and the reprogramming of immunosuppressive factors in TMEs are essential. Here, we suggest a nanoemulsion (NE)-based immunotherapeutic platform that can not only modulate tumor-induced suppression but also induce an effective cell-mediated immune response for T cell proliferation. Multifunctional NEs can be fabricated by integrating the efficacy of NEs as delivery systems and the multifaceted immunomodulation characteristics (i.e., immunostimulation and reprogramming of immunosuppression) of small molecule-based Toll-like receptor 7/8 agonists. Local in situ vaccination of melanoma and cervical tumor models with tumor antigens (protein and peptide) adjuvanted with NE loaded with TLR7/8 agonists [NE (TLR7/8a)] induced the recruitment and activation of innate immune cells, infiltration of lymphocytes, and polarization of tumor-associated M2 macrophages, which resulted in inhibition of tumor growth and prolonged survival in both primary and rechallenged tumor models. Antibody-depletion experiments also suggested that macrophages, type I IFN (IFN-α and IFN-β), CD8+ T cells, and NK1.1+ cells contributed to the antitumor effect of NE (TLR7/8a). The combination of antitumoral lymphocytes and reprogramming of immunosuppressive TMEs induced by NE (TLR7/8a) treatment evoked a synergistic antitumor immune response with immune checkpoint blockade therapy (anti-PD-1 and anti-PD-L1).
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