Phenotypic analysis of prostate-infiltrating lymphocytes reveals TH17 and Treg skewing
Phenotypic analysis of prostate-infiltrating lymphocytes reveals TH17 and Treg skewing
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DOI：
10.1158/1078-0432.ccr-07-5164
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发表时间：
2008-06-01
影响因子：
11.5
通讯作者：
Drake, Charles G.
中科院分区：
文献类型：
--
作者：
Sfanos, Karen Sandell;Bruno, Tullia C.;Drake, Charles G.
目的：前列腺癌患者切除的前列腺的病理检查通常显示浸润的CD 4（+）和CD 8（+）T细胞。鲜为人知的是，这些细胞的表型，尽管积累的证据表明慢性炎症在前列腺癌的病因学中的潜在作用。实验设计：我们开发了一种技术，通过串行针抽吸样本的大多数外周前列腺。使用磁珠分离CD 4（+）前列腺浸润淋巴细胞（PIL），并使用流式细胞术和定量逆转录PCR分析亚群偏移。荧光激活细胞分选的前列腺浸润性调节性T细胞（CD 4（+），CD 25（+），GITR（+））的转录谱与幼稚的外周血T细胞进行了比较，结果：CD 4（+）PIL显示T（H）2（白细胞介素-4-分泌）细胞的缺乏，这是一个令人惊讶的发现，因为这些细胞与慢性、阴燃性炎症的普遍接受的关联。相反，CD 4（+）PIL似乎偏向于调节性T-reg表型（FoxP 3（+））以及T（H）17表型（白细胞介素-17（+））。我们还发现T（H）17介导的炎症的优势与较低的病理Gleason评分相关。这些蛋白质水平的数据反映在信息水平，通过定量逆转录-PCR分析。前列腺浸润性T-reg的微阵列分析显示预期的T-reg相关转录本（FoxP 3、CTLA-4、GITR、LAG-3）以及许多独特的细胞表面标志物，其可用作额外的T-reg标志物。综合起来看，这些数据表明T（H）17和/或T-reg CD 4（+）T细胞（而不是T（H）2 T细胞）可能参与前列腺癌的发生或进展。
Purpose: Pathologic examination of prostate glands removed from patients with prostate cancer commonly reveals infiltrating CD4(+) and CD8(+) T cells. Little is known about the phenotype of these cells, despite accumulating evidence suggesting a potential role for chronic inflammation in the etiology of prostate cancer.Experimental Design: We developed a technique that samples the majority of the peripheral prostate through serial needle aspirates. CD4(+) prostate-infiltrating lymphocytes (PIL) were isolated using magnetic beads and analyzed for subset skewing using both flow cytometry and quantitative reverse transcription-PCR. The transcriptional profile of fluorescence-activated cell sorted prostate-infiltrating regulatory T cells (CD4(+), CD25(+), GITR(+)) was compared with naive, peripheral blood T cells using microarray analysis.Results: CD4(+) PIL showed a paucity of T(H)2 (interleukin-4-secreting) cells, a surprising finding given the generally accepted association of these cells with chronic, smoldering inflammation. Instead, CD4(+) PIL seemed to be skewed towards a regulatory T-reg phenotype (FoxP3(+)) as well as towards the T(H)17 phenotype (interleukin-17(+)). We also found that a preponderance of T(H)17-mediated inflammation was associated with a lower pathologic Gleason score. These protein level data were reflected at the message level, as analyzed by quantitative reverse transcription-PCR. Microarray analysis of pooled prostate-infiltrating T-reg revealed expected T-reg-associated transcripts (FoxP3, CTLA-4, GITR, LAG-3) as well as a number of unique cell surface markers that may serve as additional T-reg markers.Conclusion: Taken together, these data suggest that T(H)17 and/or T-reg CD4(+) T cells (rather than T(H)2 T cells) may be involved in the development or progression of prostate cancer.