Restraint and Social Isolation Stressors Differentially Regulate Adaptive Immunity and Tumor Angiogenesis in a Breast Cancer Mouse Model.
Restraint and Social Isolation Stressors Differentially Regulate Adaptive Immunity and Tumor Angiogenesis in a Breast Cancer Mouse Model.
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DOI：
10.5539/cco.v6n1p12
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发表时间：
2017-05-01
期刊：
影响因子：
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通讯作者：
Flint, Melanie S
中科院分区：
文献类型：
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作者：
Budiu, Raluca A;Vlad, Anda M;Flint, Melanie S
应激诱导免疫抑制的能力被广泛认可，但在肿瘤进展期间应激对适应性免疫系统的影响的潜在机制尚未完全理解。为了研究应激对体内免疫系统的影响，我们使用了携带4 T1乳腺癌细胞的临床前免疫活性小鼠模型。将小鼠随机分为4组，包括社会隔离（SI）、急性束缚应激（aRRS）、慢性束缚应激（cRRS）和无应激（NS）。我们发现，与NS小鼠相比，SI显著减少了在方案结束时（28天）仍然存活的荷瘤小鼠的数量。尽管我们没有检测到原发肿瘤体积的显著变化，但我们观察到SI小鼠原发肿瘤中内皮标志物CD 31以及SI和RRS小鼠肺转移瘤中内皮标志物CD 31的显著增加。SI小鼠的存活率下降与脾CD 8细胞和活化T细胞的显著减少相关。从机制的角度来看，RRS增加了小鼠肿瘤中FOXP 3、CXCL-10和颗粒酶B的表达，普萘洛尔可逆转这种作用。我们的数据表明，各种形式的压力差异影响适应性免疫和肿瘤血管生成，并对生存产生负面影响。
The ability of stress to induce immune suppression is widely recognized, but the mechanisms underlying the effects of stress on the adaptive immune system during tumor progression are not completely understood. To study the effect of stress on the immune system in vivo, we used a preclinical immunocompetent mouse model bearing 4T1 mammary adenocarcinoma cells. Mice were randomized into 4 groups, including social isolation (SI), acute restraint stress (aRRS), chronic restraint stress (cRRS), or no stress (NS). We found that SI significantly decreased the number of tumor-bearing mice still alive at the end of protocol (28 days), compared to NS mice. Although we did not detect significant changes in primary tumor volume, we observed a significant increase in the endothelial marker CD31 in primary tumors of SI mice and in lung metastases in SI and RRS mice. Survival decline in SI mice was associated with significant decreases in splenic CD8 cells and in activated T cells. From a mechanistic standpoint, RRS increased expression of FOXP3, CXCL-10, and granzyme B in mouse tumors, and the effects were reversed by propranolol. Our data demonstrate that various forms of stress differentially impact adaptive immunity and tumor angiogenesis, and negatively impact survival.