实体周边肿瘤如何影响脑部神经免疫反应尚不清楚，尽管癌症患者报告了各种脑介导的副作用和更高的感染率。我们假设慢性低级别的周边肿瘤诱导炎症刺激状态的微胶质细胞，从而抑制对后续周边免疫挑战的神经炎症反应。在这里，我们使用Balb / c乳房癌小鼠，观察到对脂多糖（LPS）和活的大肠杆菌（E. coli）挑战以及对E. coli感染的疲劳反应，Balb / c小鼠微胶质细胞炎症基因表达反应下降。相比之下，与无肿瘤小鼠相比，在回收的原始小胶质细胞培养中，对LPS或toll样受体2激动剂的炎症基因表达反应，以及对侧脑室注射IL-1β的神经炎症和病态行为反应是相似的。这些数据支持假设：Balb / c乳腺肿瘤通过抑制周边体液反应的机制，减弱对免疫挑战的神经炎症反应。 Balb / c乳腺肿瘤略微减弱了对LPS和E. coli挑战的选择循环细胞因子反应。此外，另一个乳腺肿瘤/小鼠品系模型（C57Bl / 6小鼠的E0771肿瘤）对免疫挑战显示出轻微的炎性反应增加。综上所述，这些数据表明，肿瘤诱导的神经炎症和疾病行为的抑制可能是由于微胶质细胞表型的减弱，部分原因是外周信号到达大脑的下降，这可能有助于癌症患者报告的感染反应和行为副作用。最后，这些神经免疫效应可能因肿瘤类型和/或宿主免疫表型而异。

It is poorly understood how solid peripheral tumors affect brain neuroimmune responses despite the various brain-mediated side effects and higher rates of infection reported in cancer patients. We hypothesized that chronic low-grade peripheral tumor-induced inflammation conditions microglia to drive suppression of neuroinflammatory responses to a subsequent peripheral immune challenge. Here, Balb/c murine mammary tumors attenuated the microglial inflammatory gene expression responses to lipopolysaccharide (LPS) and live Escherichia coli (E. coli) challenges and the fatigue response to an E. coli infection. In contrast, the inflammatory gene expression in response to LPS or a toll-like receptor 2 agonist of Percoll-enriched primary microglia cultures was comparable between tumor-bearing and -free mice, as were the neuroinflammatory and sickness behavioral responses to an intracerebroventricular interleukin (IL)-1β injection. These data led to the hypothesis that Balb/c mammary tumors blunt the neuroinflammatory responses to an immune challenge via a mechanism involving tumor suppression of the peripheral humoral response. Balb/c mammary tumors modestly attenuated select circulating cytokine responses to LPS and E. coli challenges. Further, a second mammary tumor/mouse strain model (E0771 tumors in C57Bl/6 mice) displayed mildly elevated inflammatory responses to an immune challenge. Taken together, these data indicate that tumor-induced suppression of neuroinflammation and sickness behaviors may be driven by a blunted microglial phenotype, partly due to an attenuated peripheral signal to the brain, which may contribute to infection responses and behavioral side effects reported in cancer patients. Finally, these neuroimmune effects likely vary based on tumor type and/or host immune phenotype.This article is protected by copyright. All rights reserved.