Tumor escape mechanisms: potential role of soluble HLA antigens and NK cells activating ligands.
Tumor escape mechanisms: potential role of soluble HLA antigens and NK cells activating ligands.
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DOI：
10.1111/j.1399-0039.2008.01106.x
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发表时间：
2008-10
期刊：
影响因子：
--
通讯作者：
Ferrone S
中科院分区：
文献类型：
--
作者：
Campoli M;Ferrone S
HLA抗原和自然杀伤（NK）细胞活化配体在恶性细胞与宿主免疫系统组分的相互作用中所起的关键作用已经激发了对恶性细胞表达的表征的兴趣。用识别HLA抗原和NK细胞活化配体的单克隆抗体（mAb）对手术切除的恶性病变进行免疫组织化学染色产生的令人信服的证据表明，这些分子的表面表达在恶性细胞上经常改变。这些变化似乎具有临床意义，因为在某些类型的恶性疾病中，它们与病变的组织病理学特征以及无病间期和生存期相关。这些协会已被建议反映HLA抗原和NK细胞活化配体异常对肿瘤细胞与抗原特异性细胞毒性T淋巴细胞（CTL）和NK细胞的相互作用的影响。然而，存在这样的实例，其中在所研究的患者中，疾病在面对适当的HLA抗原和/或NK细胞活化配体以及恶性细胞的肿瘤抗原表达和功能性抗原特异性CTL的情况下进展。在这种情况下，肿瘤微环境可能不利于CTL和NK细胞活性，并有助于肿瘤免疫逃逸。许多独特的逃逸机制已被证明可以保护恶性细胞免受肿瘤微环境中的免疫识别和破坏。在本文中，可溶性HLA抗原和NK细胞活化配体的结构和功能特性的描述，我们将审查在恶性疾病中的血清水平的变化，并讨论其潜在的作用，在逃避机制所利用的肿瘤细胞，以避免识别和破坏。
The crucial role played by HLA antigens and natural killer (NK) cell activating ligands in the interactions of malignant cells with components of the host's immune system has stimulated interest in the characterization of their expression by malignant cells. Convincing evidence generated by the immunohistochemical staining of surgically removed malignant lesions with monoclonal antibodies (mAb) recognizing HLA antigens and NK cell activating ligands indicates that the surface expression of these molecules is frequently altered on malignant cells. These changes appear to have clinical significance, since in some types of malignant disease they are associated with the histopathological characteristics of the lesions as well as with disease free interval and survival. These associations have been suggested to reflect the effect of HLA antigen and NK cell activating ligand abnormalities on the interactions of tumor cells with antigen-specific cytotoxic T lymphocytes (CTL) and with NK cells. Nevertheless, there are examples in which disease progresses in the face of appropriate HLA antigen and/or NK cell activating ligand as well as tumor antigen expression by malignant cells and of functional antigen-specific CTL in the investigated patient. In such scenarios, it is likely that the tumor microenvironment is unfavorable for CTL and NK cell activity and contributes to tumor immune escape. Many distinct escape mechanisms have been shown to protect malignant cells from immune recognition and destruction in the tumor microenvironment. In this paper, following the description of the structural and functional characteristics of soluble HLA antigens and NK cell activating ligands, we will review changes in their serum level in malignant disease and discuss their potential role in the escape mechanisms utilized by tumor cells to avoid recognition and destruction.
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