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前列腺癌瘤内CD8 +调节性T细胞的临床意义

Clinical significance of intratumoral CD8+ regulatory T cells in prostate carcinoma.

作者信息

Compérat Eva, Egevad Lars, Camparo Philippe, Roupret Morgan, Vaessen Christophe, Valdman Alexander, Jonmarker Sara, Capron Fréderique, Cussenot Olivier, Charlotte Fréderic

机构信息

Pathologic Anatomy Service and Urology Service, Hôpital La Pitié-Salpêtrière, AP-HP, Université Pierre et Marie Curie, Parie, Frances.

出版信息

Anal Quant Cytol Histol. 2010 Feb;32(1):39-44.

PMID:20701086
Abstract

OBJECTIVE

To explore Foxp3, a member of the forkhead box family of transcription factors, which is a major gene for regulatory T (Treg) cell development of CD4+CD25+ or CD8+CD25+ phenotype.

STUDY DESIGN

We constructed tissue microarrays from 82 patients after radical prostatectomy (RP). Three cores of neoplastic tissue and 3 from normal/inflammatory tissue were taken. Sections were immunostained for Foxp3 and CD8. Numbers of Foxp3 and CD8 positive cells were counted. Serum prostate-specific antigen levels before and after RP, Gleason score (GS), surgical margin status and pathologic stage were available.

RESULTS

Among 82 patients aged 55-76 years (mean 66.1, SD +/- 5.8), 64 (78%) were staged pT2 and 18 (22%) pT3. Twenty-nine patients (35%) had positive margins, 24 (29%) increasing prostate-specific antigen levels (biochemical relapse) 6 months to 2 years (SD +/- 24.8 months) after RP. GS was distributed as follows: 41 (50%) patients with GS 6 (3+3), 34 (41%) with GS 7 [19 (3+4) and 15 (4+3)], 7 (9%) with GS > or = 8. In tumor cores, Foxp3 and CD8 counts correlated (p = 0.012). Foxp3 counts also correlated with biochemical relapse (p = 0.04).

CONCLUSION

Treg cells were more common in cancer than in benign prostatic tissue. There are links between Foxp3 and CD8+ cells and between Foxp3 positive cells and biochemical relapse. Patients with prostate cancer show an immunosuppressive regulatory profile, including nonresponsive Tregs. It would be important to find mechanisms to target these cells for successful immunotherapy.

摘要

目的

探讨叉头框转录因子家族成员Foxp3,其是CD4+CD25+或CD8+CD25+表型调节性T(Treg)细胞发育的主要基因。

研究设计

我们从82例行前列腺癌根治术(RP)的患者中构建组织芯片。取3个肿瘤组织核心和3个正常/炎症组织核心。切片进行Foxp3和CD8免疫染色。计数Foxp3和CD8阳性细胞数量。可获得RP前后的血清前列腺特异性抗原水平、Gleason评分(GS)、手术切缘状态和病理分期。

结果

82例年龄在55 - 76岁(平均66.1岁,标准差±5.8)的患者中,64例(7�%)为pT2期,18例(22%)为pT3期。29例(35%)切缘阳性,24例(29%)在RP后6个月至2年(标准差±24.8个月)出现前列腺特异性抗原水平升高(生化复发)。GS分布如下:41例(50%)患者GS为6(3 + 3),34例(41%)患者GS为7 [19例(3 + 4)和15例(4 + 3)],7例(9%)患者GS≥8。在肿瘤核心中,Foxp3和CD8计数相关(p = 0.012)。Foxp3计数也与生化复发相关(p = 0.04)。

结论

Treg细胞在癌组织中比在良性前列腺组织中更常见。Foxp3与CD8+细胞之间以及Foxp3阳性细胞与生化复发之间存在联系。前列腺癌患者表现出免疫抑制调节特征,包括无反应性Treg。找到针对这些细胞的机制以实现成功的免疫治疗将很重要。

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