期刊
ACS APPLIED MATERIALS & INTERFACES
卷 11, 期 2, 页码 1876-1885出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.8b18751
关键词
combinatorial immunotherapy; PD-L1; IDO inhibition; photothermal therapy; reduced graphene oxide
资金
- National Natural Science Foundation of China [81673027, 31670948, 31600743]
- Tianjin Natural Science Fund for Distinguished Young Scholars [17JCJQJC46400]
- CAMS Innovation Fund for Medical Sciences [CAMS-I2M-3-026]
- Specific Program for High-Tech Leader AMP
- Team of Tianjin Government
Despite the potential efficacy of immune checkpoint blockade for effective treatment of cancer, this therapeutic modality is not generally curative, and only a fraction of patients respond. Combination approaches provide strategies to target multiple antitumor immune pathways to induce synergistic antitumor immunity. Here, a multi-combination immunotherapy, including photothermal therapy (PTT), indoleamine-2,3-dioxygenase (IDO) inhibition, and programmed cell death-ligand 1 (PD-L1) blockade, is introduced for inducing synergistic antitumor immunity. We designed a multifunctional IDO inhibitor (IDOi)-loaded reduced graphene oxide (rGO)-based nanosheets (IDOi/rGO nanosheets) with the properties to directly kill tumor cells under laser irradiation and in situ trigger antitumor immune response. In vivo experiments further revealed that the triggered immune response can be synergistically promoted by IDO inhibition and PD-L1 blockade; the responses included the enhancement of tumor-infiltrating lymphocytes, including CD45(+) leukocytes, CD4(+) T cells, CD8(+) T cells, and NK cells; the inhibition of the immune suppression activity of regulator T cells (T-rcgs); and the production of INF-gamma. We also demonstrate that the three combinations of PTT, IDO inhibition, and PD-L1 blockade can effectively inhibit the growth of both irradiated tumors and tumors in distant sites without PTT treatment. This work can be thought of as an important proof of concept to target multiple antitumor immune pathways to induce synergistic antitumor immunity.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据