Departments of Ophthalmology, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
Invest Ophthalmol Vis Sci. 2012 Aug 9;53(9):5370-8. doi: 10.1167/iovs.11-9280.
In contrast to many other malignancies, in uveal melanoma (UM) the presence of an immune infiltrate is associated with a bad prognosis. An analysis of the different functional phenotypes of tumor-infiltrating leukocytes (TIL) and a comparison with the genetic background of the tumors may help to explain this apparent anomaly.
We performed a comprehensive immunohistochemical study by evaluating the density of CD8(+) and CD4(+) T lymphocytes, forkhead box p3 (Foxp3(+)) regulatory T cells (Tregs), and CD68(+) and CD68(+)CD163(+) macrophages in 43 cases of UM in relation to tumor characteristics. Expression of the chemokines CCL2, CCL17, and CCL22 in cultured human UM cells and peripheral blood monocytes was analyzed by quantitative PCR (qPCR).
The presence of TILs was highly variable between tumors and was dominated by CD8(+) T cells with fewer CD4(+) T cells and Tregs. When tumors were infiltrated by immune cells, the infiltrate generally comprised all different subsets of lymphocytes (P < 0.001) and M2 macrophages (P < 0.001). Different T-cell ratios did not influence clinical outcome. In addition, the presence of TIL correlated with the loss of one chromosome 3 (P < 0.04). UM cells express CCL2 and CCL22, two chemokines known to mediate trafficking of immune cells to the tumor.
All studied subtypes of tumor-infiltrating immune cells were collectively increased and showed an association with monosomy of chromosome 3 suggesting that tumor intrinsic factors control the leukocyte influx, possibly through local chemokine secretion.
与许多其他恶性肿瘤不同，葡萄膜黑色素瘤（UM）中存在免疫浸润与预后不良相关。分析肿瘤浸润白细胞（TIL）的不同功能表型，并与肿瘤的遗传背景进行比较，可能有助于解释这种明显的异常。
我们通过评估 43 例 UM 肿瘤中 CD8(+)和 CD4(+)T 淋巴细胞、叉头框 p3(Foxp3(+))调节性 T 细胞（Tregs）以及 CD68(+)和 CD68(+)CD163(+)巨噬细胞的密度，与肿瘤特征相关，进行了全面的免疫组织化学研究。通过定量 PCR（qPCR）分析培养的人 UM 细胞和外周血单核细胞中趋化因子 CCL2、CCL17 和 CCL22 的表达。
TIL 的存在在肿瘤之间差异很大，以 CD8(+)T 细胞为主，CD4(+)T 细胞和 Tregs 较少。当肿瘤被免疫细胞浸润时，浸润通常包含所有不同的淋巴细胞亚群（P < 0.001）和 M2 巨噬细胞（P < 0.001）。不同的 T 细胞比例不会影响临床结果。此外，TIL 的存在与一条 3 号染色体的缺失相关（P < 0.04）。UM 细胞表达 CCL2 和 CCL22，这两种趋化因子已知可介导免疫细胞向肿瘤转移。
所有研究的肿瘤浸润免疫细胞亚群均增加，并与 3 号染色体单体缺失相关，表明肿瘤内在因素控制白细胞浸润，可能通过局部趋化因子分泌。
