de Waard-Siebinga I, Hilders C G, Hansen B E, van Delft J L, Jager M J
Department of Ophthalmology, University Hospital Leiden, The Netherlands.
Graefes Arch Clin Exp Ophthalmol. 1996 Jan;234(1):34-42. doi: 10.1007/BF00186516.
In uveal melanoma, both the amount of tumor-infiltrating cells and the level of expression of HLA antigens are quite variable. We hypothesized that low levels of HLA expression lead to a lack of antigen presentation, which might prevent proper immunologic recognition of the tumor. This lack of recognition might subsequently lead to low levels of tumor-infiltrating cells.
To test this hypothesis, we determined the type and number of tumor-infiltrating cells in tumor sections from 24 uveal melanomas. We applied monoclonal antibodies directed against different types of immune cells and compared the results with the expression of HLA class I and class II antigens on the tumor cells.
Infiltrating immune cells were observed in all uveal melanomas (although in small amounts), with a predominance of T lymphocytes. Significant positive correlations were observed between the number of CD3+ cells (T lymphocytes) and monomorphic HLA class I expression, allele-specific HLA-A2 and Bw4 expression, and HLA class II expression. Furthermore, the number of CD4+ cells (T helper cells, monocytes/ macrophages) and of CD11b+ cells (monocytes/macrophages) was significantly correlated with the level of monomorphic HLA class I expression.
These data support our hypothesis that low levels of HLA expression (and therefore a lack of presentation of tumor-specific antigens) may lead to a low level of tumor infiltrate.
在葡萄膜黑色素瘤中,肿瘤浸润细胞的数量和HLA抗原的表达水平差异很大。我们推测HLA低表达导致抗原呈递缺乏,这可能会阻止对肿瘤的正常免疫识别。这种识别缺乏可能随后导致肿瘤浸润细胞水平降低。
为了验证这一假设,我们确定了24例葡萄膜黑色素瘤肿瘤切片中肿瘤浸润细胞的类型和数量。我们应用针对不同类型免疫细胞的单克隆抗体,并将结果与肿瘤细胞上HLA I类和II类抗原的表达进行比较。
在所有葡萄膜黑色素瘤中均观察到浸润性免疫细胞(尽管数量较少),以T淋巴细胞为主。观察到CD3 +细胞(T淋巴细胞)的数量与单态性HLA I类表达、等位基因特异性HLA - A2和Bw4表达以及HLA II类表达之间存在显著正相关。此外,CD4 +细胞(辅助性T细胞、单核细胞/巨噬细胞)和CD11b +细胞(单核细胞/巨噬细胞)的数量与单态性HLA I类表达水平显著相关。
这些数据支持我们的假设,即HLA低表达(因此缺乏肿瘤特异性抗原呈递)可能导致肿瘤浸润水平降低。