Le Naour Julie, Galluzzi Lorenzo, Zitvogel Laurence, Kroemer Guido, Vacchelli Erika
Equipe Labellisée Par La Ligue Contre Le Cancer, Université De Paris, Sorbonne Université, INSERM U1138, Centre De Recherche Des Cordeliers, Paris, France.
Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France.
Oncoimmunology. 2020 Jun 2;9(1):1771143. doi: 10.1080/2162402X.2020.1771143.
Toll-like receptor 3 (TLR3) is a pattern recognition receptor that senses exogenous (viral) as well as endogenous (mammalian) double-stranded RNA in endosomes. On activation, TLR3 initiates a signal transduction pathway that culminates with the secretion of pro-inflammatory cytokines including type I interferon (IFN). The latter is essential not only for innate immune responses to infection but also for the initiation of antigen-specific immunity against viruses and malignant cells. These aspects of TLR3 biology have supported the development of various agonists for use as stand-alone agents or combined with other therapeutic modalities in cancer patients. Here, we review recent preclinical and clinical advances in the development of TLR3 agonists for oncological disorders.
cDC, conventional dendritic cell; CMT, cytokine modulating treatment; CRC, colorectal carcinoma; CTL, cytotoxic T lymphocyte; DC, dendritic cell; dsRNA, double-stranded RNA; FLT3LG, fms-related receptor tyrosine kinase 3 ligand; HNSCC, head and neck squamous cell carcinoma; IFN, interferon; IL, interleukin; ISV, vaccine; MUC1, mucin 1, cell surface associated; PD-1, programmed cell death 1; PD-L1, programmed death-ligand 1; polyA:U, polyadenylic:polyuridylic acid; polyI:C, polyriboinosinic:polyribocytidylic acid; TLR, Toll-like receptor.
Toll样受体3（TLR3）是一种模式识别受体，可在内体中感知外源性（病毒）和内源性（哺乳动物）双链RNA。激活后，TLR3启动一条信号转导通路，最终导致包括I型干扰素（IFN）在内的促炎细胞因子分泌。后者不仅对感染的先天免疫反应至关重要，而且对针对病毒和恶性细胞的抗原特异性免疫的启动也至关重要。TLR3生物学的这些方面支持了各种激动剂的开发，这些激动剂可作为单独的药物使用，或与其他治疗方式联合用于癌症患者。在这里，我们综述了TLR3激动剂在肿瘤疾病治疗方面的最新临床前和临床进展。
cDC，常规树突状细胞；CMT，细胞因子调节治疗；CRC，结直肠癌；CTL，细胞毒性T淋巴细胞；DC，树突状细胞；dsRNA，双链RNA；FLT3LG，fms相关受体酪氨酸激酶3配体；HNSCC，头颈部鳞状细胞癌；IFN，干扰素；IL，白细胞介素；ISV，疫苗；MUC1，粘蛋白1，细胞表面相关；PD-1，程序性细胞死亡蛋白1；PD-L1，程序性死亡配体1；聚A:U，聚腺苷酸:聚尿苷酸；聚肌胞苷酸，聚肌苷酸:聚胞苷酸；TLR，Toll样受体。
