Fischell Department of Bioengineering, University of Maryland, 8278 Paint Branch Drive, College Park, MD 20742, USA.
Fischell Department of Bioengineering, University of Maryland, 8278 Paint Branch Drive, College Park, MD 20742, USA; Robert E. Fischell Institute for Biomedical Devices, 8278 Paint Branch Drive, College Park, MD 20742, USA; United States Department of Veterans Affairs, Maryland VA Health Care System, 10 North Greene Street, Baltimore, MD 21201, USA; Department of Microbiology and Immunology, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201, USA; Marlene and Stewart Greenebaum Cancer Center, 22 South Greene Street, Baltimore, MD 21201, USA.
Curr Opin Biotechnol. 2019 Dec;60:138-145. doi: 10.1016/j.copbio.2019.01.010. Epub 2019 Mar 1.
A key challenge facing immunotherapy is poor infiltration of T cells into tumors, along with suppression of cells reaching these sites. However, macrophages make up a majority of immune cell infiltrates into tumors, creating natural targets for immunotherapies able to direct macrophages away from tumor-supportive functions and toward anti-tumor phenotypes. Recent studies demonstrate that toll-like receptors (TLRs) - pathways that quickly trigger early immune responses - play an important role in polarizing macrophages. Here, we present emerging ways in which TLR signaling is being manipulated in macrophages to create new opportunities for cancer immunotherapy. In particular, we discuss approaches to deliver TLR agonists, to leverage biomaterials in these therapies, and to couple TLR-based approaches with other frontline treatments as combination cancer therapies.
免疫疗法面临的一个主要挑战是 T 细胞难以浸润肿瘤，以及到达这些部位的细胞受到抑制。然而，巨噬细胞在肿瘤中的免疫细胞浸润中占多数，为能够使巨噬细胞远离肿瘤支持功能并向抗肿瘤表型转变的免疫疗法提供了天然靶点。最近的研究表明， Toll 样受体 (TLR) - 快速引发早期免疫反应的途径 - 在巨噬细胞的极化中起着重要作用。在这里，我们介绍了目前正在巨噬细胞中操纵 TLR 信号的新方法，为癌症免疫疗法创造了新的机会。特别是，我们讨论了递送 TLR 激动剂的方法，利用这些疗法中的生物材料，以及将 TLR 为基础的方法与其他一线治疗方法相结合作为联合癌症治疗方法。
