Abstract：
Agents that induce inflammation have been used since the 18th century for the treatment of cancer. The inflammation induced by agents such as Toll-like receptor agonists is thought to stimulate tumor-specific immunity in patients and augment control of tumor burden. While NOD-scid IL2rγnull mice lack murine adaptive immunity (T cells and B cells), these mice maintain a residual murine innate immune system that responds to Toll-like receptor agonists. Here we describe a novel NOD-scid IL2rγnull mouse lacking murine TLR4 that fails to respond to lipopolysaccharide. NSG-Tlr4null mice support human immune system engraftment and enable the study of human-specific responses to TLR4 agonists in the absence of the confounding effects of a murine response. Our data demonstrate that specific stimulation of TLR4 activates human innate immune systems and delays the growth kinetics of a human patient-derived xenograft melanoma tumor.
摘要：
自18世纪以来，诱导炎症的药物已用于治疗癌症。由诸如Toll样受体激动剂的药剂诱导的炎症被认为刺激患者的肿瘤特异性免疫并增强肿瘤负荷的控制。虽然NOD-scidIL2rγnull小鼠缺乏小鼠适应性免疫（T细胞和B细胞），这些小鼠维持对Toll样受体激动剂有反应的残余鼠先天性免疫系统.在这里，我们描述了一种缺乏鼠TLR4的新型NOD-scidIL2rγnull小鼠，它对脂多糖没有反应。NSG-Tlr4null小鼠支持人类免疫系统植入，并能够在不存在鼠反应的混杂作用的情况下研究对TLR4激动剂的人类特异性反应。我们的数据表明，TLR4的特异性刺激激活人类先天免疫系统并延迟人类患者来源的异种黑色素瘤肿瘤的生长动力学。
