Directing toll-like receptor signaling in macrophages to enhance tumor immunotherapy.
Directing toll-like receptor signaling in macrophages to enhance tumor immunotherapy.
复制标题
DOI：
10.1016/j.copbio.2019.01.010
复制
发表时间：
2019-12
影响因子：
7.7
通讯作者：
Qin Zeng;C. Jewell
中科院分区：
文献类型：
--
作者：
Qin Zeng;C. Jewell
巨噬细胞是独特的靶标，因为它们能自然浸润肿瘤。巨噬细胞可以表现出肿瘤支持或抗肿瘤表型。TLR信号在巨噬细胞极化表型中起重要作用。生物材料极化巨噬细胞的内在特性和通过传递TLRa。将基于tlr的治疗方法与现有方法相结合可以产生协同效应。免疫疗法面临的一个关键挑战是T细胞对肿瘤的浸润不良，以及到达这些部位的细胞受到抑制。然而，巨噬细胞构成了大多数渗透到肿瘤中的免疫细胞，为能够引导巨噬细胞远离肿瘤支持功能而转向抗肿瘤表型的免疫疗法创造了天然靶点。最近的研究表明，toll样受体(TLRs) -快速触发早期免疫反应的途径-在巨噬细胞极化中起重要作用。在这里，我们提出了巨噬细胞中TLR信号被操纵的新方法，为癌症免疫治疗创造了新的机会。我们特别讨论了TLR激动剂的使用方法，在这些治疗中利用生物材料，以及将基于TLR的方法与其他一线治疗结合起来作为联合癌症治疗。
HighlightsMacrophages are unique targets because they naturally infiltrate tumors.Macrophages can exhibit tumor-supportive or anti-tumor phenotypes.TLR signaling plays a significant role in polarizing macrophage phenotype.Biomaterials polarize macrophages with intrinsic properties and by delivery of TLRa.Combining TLR-based therapies with existing approaches creates synergies.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.