Lagouros Evan, Salomao Diva, Thorland Erik, Hodge David O, Vile Richard, Pulido Jose S
Departments of Ophthalmology, Mayo Clinic, Rochester, Minnesota, USA.
Trans Am Ophthalmol Soc. 2009 Dec;107:223-8.
The role of T regulatory (Treg) cells in blunting immune response to cancer appears to be significant, but the presence of Treg cells in uveal melanoma has not been extensively examined. We therefore evaluated the presence of tumor-infiltrating Treg cells in uveal melanomas.
A retrospective search of Mayo Clinic records from 2000 to 2005 was performed to identify cases of eyes enucleated as a consequence of uveal melanoma. Histologic examination included location of the tumor, presence of emissary canal invasion, direct sclera extension, extraocular extension, cell type and predominant cell type, mitotic figures per 40 high-power fields, lymphocytic tumor invasion, necrosis, microvascular pattern, and presence of CD3, CD4, CD25, and Foxp3cells. Factors obtained by chart review were also evaluated, including clinical size and ultrasound thickness of tumor before enucleation, patient age at time of enucleation, systemic evaluation for metastatic disease both before and after enucleation, monosomy 3, and systemic status at last patient visit.
Of 42 enucleated eyes, 17 (40.5 %) were found to have lymphocytic infiltrate and 5 (11.9%) were considered positive for the presence of Treg cells (CD3+CD4+CD25+Foxp3+ or CD3+CD4+CD25-Foxp3+). Thus 29.4% (5 of 17) of those with lymphocytic infiltates had Treg cells, and 4 of the 5 with Treg cells had a large lymphocytic infiltrate (>1400 CD3 cells). When using "death due to disease" as the hazard ratio (HR) end point, the HR for presence of CD3 was 5.5 (P = .03) and for clinical size, 1.2 (P = .03). Furthermore, when using "presence of metastasis" as the end point, the HR for presence of CD3 was 3.6 (P = .05) and for clinical size, 1.3 (P = .003).
Though T lymphocyte infiltration is a bad prognostic indicator, Treg cells are rarely seen in enucleated choroidal melanoma, so their local effect may be limited in contradistinction to other cancers.
调节性T（Treg）细胞在减弱对癌症的免疫反应中所起的作用似乎很重要，但葡萄膜黑色素瘤中Treg细胞的存在尚未得到广泛研究。因此，我们评估了葡萄膜黑色素瘤中肿瘤浸润性Treg细胞的存在情况。
对梅奥诊所2000年至2005年的记录进行回顾性检索，以确定因葡萄膜黑色素瘤而摘除眼球的病例。组织学检查包括肿瘤的位置、有无引流管浸润、直接巩膜扩展、眼外扩展、细胞类型和主要细胞类型、每40个高倍视野中的有丝分裂象、淋巴细胞肿瘤浸润、坏死、微血管模式以及CD3、CD4、CD25和Foxp3细胞的存在情况。还评估了通过病历审查获得的因素，包括摘除眼球前肿瘤的临床大小和超声厚度、摘除眼球时患者的年龄、摘除眼球前后的转移性疾病全身评估、三体性3以及最后一次患者就诊时的全身状况。
在42只摘除的眼球中，17只（40.5%）有淋巴细胞浸润，5只（11.9%）被认为存在Treg细胞（CD3+CD4+CD25+Foxp3+或CD3+CD4+CD25-Foxp3+）呈阳性。因此，在有淋巴细胞浸润的患者中，29.4%（17例中的5例）有Treg细胞，在5例有Treg细胞的患者中，有4例有大量淋巴细胞浸润（>1400个CD3细胞）。以“疾病导致的死亡”作为风险比（HR）终点时，CD3存在的HR为5.5（P = 0.03），临床大小的HR为1.2（P = 0.03）。此外，以“转移的存在”作为终点时，CD3存在的HR为3.6（P = 0.05），临床大小的HR为1.3（P = 0.003）。
虽然T淋巴细胞浸润是一个不良预后指标，但在摘除的脉络膜黑色素瘤中很少见到Treg细胞，因此与其他癌症相比，它们的局部作用可能有限。
