HLA‐DRB alleles are differentially expressed by tumor cells in breast carcinoma
HLA‐DRB alleles are differentially expressed by tumor cells in breast carcinoma
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DOI：
10.1002/ijc.20441
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发表时间：
2004-11
影响因子：
6.4
通讯作者：
S. Oldford;J. Robb;P. Watson;S. Drover
中科院分区：
文献类型：
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作者：
S. Oldford;J. Robb;P. Watson;S. Drover
人类白细胞抗原-DR的表达和T细胞在乳腺癌中的侵袭在生物学和预后方面的意义目前尚存争议。为了验证这些因素受特定的HLA-DRB等位基因影响的假设，采用免疫组织化学方法检测了52例乳腺肿瘤标本中DR及其相关不变链(II)的表达和CD3+T细胞的浸润情况。肿瘤细胞DR的表达与T细胞的浸润显著相关，而DRB1*04肿瘤中DR+II+的比例高于非DRB1*04肿瘤，且CD3+浸润物较少。这种差异主要归因于DRB1*07肿瘤，典型的是DR−II−，尽管它们含有类似于DR+II+肿瘤的T细胞数量。用同种异型识别抗体进一步分析DR+肿瘤，发现DRB1*04等位基因总是表达，而非DRB1*04等位基因表达不一致。这项研究的结果首次提供了DRB等位基因影响乳腺癌DR表达和T细胞浸润的证据，并提示多种因素参与了DR的表达。正在进行的研究旨在阐明控制DR差异表达的分子和免疫学机制，以及对预后和结局的影响，这将进一步加深我们对肿瘤细胞所采用的抗肿瘤免疫反应和逃避策略的理解。©2004 Wiley-Liss Inc.
The biologic and prognostic significance of HLA‐DR expression and T‐cell infiltration in breast carcinoma are presently controversial. To test the hypothesis that these factors are influenced by particular HLA‐DRB alleles, 52 breast tumor samples, composed of 26 DRB1*04 and 26 non‐DRB1*04 tumors, were assessed using immunohistochemistry for expression of DR and its associated invariant chain (Ii) and for infiltrating CD3+ T cells. While DR expression by tumor cells was significantly associated with T‐cell infiltration, DRB1*04 tumors were more frequently DR+Ii+ and contained smaller CD3+ infiltrates than non‐DRB1*04 tumors. This difference was largely attributable to DRB1*07 tumors, which were typically DR−Ii−, although they contained similar numbers of T cells to DR+Ii+ tumors. Further analysis of DR+ tumors using allotype discriminating antibodies revealed that DRB1*04 alleles were always expressed, while non‐DRB1*04 alleles were inconsistently expressed. The results of this study provide the first reported evidence that DRB alleles influence DR expression and T‐cell infiltration in breast carcinoma and suggest that multiple factors contribute to DR expression. Ongoing studies aimed at elucidating the molecular and immunologic mechanisms controlling differential DR expression and implications for prognosis and outcome should further our understanding of the antitumor immune response and evasion strategies employed by tumor cells. © 2004 Wiley‐Liss, Inc.