Melanoma brain metastasis globally reconfigures chemokine and cytokine profiles in patient cerebrospinal fluid.
Melanoma brain metastasis globally reconfigures chemokine and cytokine profiles in patient cerebrospinal fluid.
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DOI：
10.1097/cmr.0000000000000045
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发表时间：
2014-04
影响因子：
2.2
通讯作者：
Wong ET
中科院分区：
文献类型：
--
作者：
Lok E;Chung AS;Swanson KD;Wong ET
黑色素瘤的侵袭性被认为与肿瘤基质相关的免疫细胞相关。细胞因子和趋化因子的作用是招募并调节这些细胞的活性，最终影响疾病的进展。由于黑色素瘤经常转移到大脑，我们询问是否可以在黑色素瘤患者的脑脊液（CSF）中检测到免疫因子谱的全球差异，并揭示与患者结局相关的肿瘤生物学方面。因此，我们测量了黑色素瘤患者CSF中12种细胞因子和12种趋化因子的水平，并对所得数据进行分析以开发无监督的分层聚类图和热图。出乎意料的是，在这些样本中发现的免疫因子的总体概况显示了它们在黑色素瘤患者CSF中表达的一般性重新配置，导致患有黑色素瘤脑转移的个体与非疾病对照分离。趋化因子CCL22和细胞因子IL 1 α、IL 4和IL 5在大多数样品中减少，而包括CXCL10、CCL4、CCL17和IL 8的子集显示表达增加。此外，对黑色素瘤患者集内确定的聚类分析比较患者结局表明，IL 1 α、IL 4、IL 5和CCL 22的抑制以及CXCL 10、CCL 4和CCL 17的伴随升高可能与脑转移的侵袭性发展相关。这些结果表明，在主机的全球免疫抑制因子，以及特定的趋化因子的选择性增加，构成了黑色素瘤脑转移瘤的主要免疫调节功能。这些改变可能会推动这种疾病在大脑中的进程，个体患者免疫特征的变化可能会预测结果。
The aggressiveness of melanoma is believed to be correlated with tumor–stroma-associated immune cells. Cytokines and chemokines act to recruit and then modulate the activities of these cells, ultimately affecting disease progression. Because melanoma frequently metastasizes to the brain, we asked whether global differences in immunokine profiles could be detected in the cerebrospinal fluid (CSF) of melanoma patients and reveal aspects of tumor biology that correlate with patient outcomes. We therefore measured the levels of 12 cytokines and 12 chemokines in melanoma patient CSF and the resulting data were analyzed to develop unsupervised hierarchical clustergrams and heat maps. Unexpectedly, the overall profiles of immunokines found in these samples showed a generalized reconfiguration of their expression in melanoma patient CSF, resulting in the segregation of individuals with melanoma brain metastasis from nondisease controls. Chemokine CCL22 and cytokines IL1α, IL4, and IL5 were reduced in most samples, whereas a subset including CXCL10, CCL4, CCL17, and IL8 showed increased expression. Further, analysis of clusters identified within the melanoma patient set comparing patient outcome suggests that suppression of IL1α, IL4, IL5, and CCL22, with concomitant elevation of CXCL10, CCL4, and CCL17, may correlate with more aggressive development of brain metastasis. These results suggest that global immunokine suppression in the host, together with a selective increase in specific chemokines, constitute a predominant immunomodulatory feature of melanoma brain metastasis. These alterations likely drive the course of this disease in the brain and variations in the immune profiles of individual patients may predict outcomes.