Molecular mechanisms of MHC class I abnormalities and APM components in human tumors
Molecular mechanisms of MHC class I abnormalities and APM components in human tumors
复制标题
DOI：
10.1007/s00262-008-0515-4
复制
发表时间：
2008-11-01
影响因子：
5.8
通讯作者：
Seliger, Barbara
中科院分区：
文献类型：
--
作者：
Seliger, Barbara
肿瘤免疫逃逸在癌症中起着关键作用，但这一过程中涉及的机制仍有待确定。近年来，在理解由MHC I类分子呈递的肽是如何产生的方面取得了进展，特别是哪些蛋白酶参与该过程以及细胞内途径如何影响专职抗原呈递细胞和各种类型的恶性肿瘤中的抗原呈递。在不同来源的实体瘤中发现了不同的MHC I类异常，但在造血系统疾病中也发现了不同的MHC I类异常。这些包括结构改变，如MHC I类重链的总缺失、单倍型缺失和等位基因缺失，缺失和点突变，特别是β 2-微球蛋白和TAP 1，以及MHC I类抗原加工机制（APM）的各种组分的失调，这些可能发生在表观遗传、转录和转录后水平。MHC I类抗原加工途径的单个或多个组分的表达的缺乏或下调可能避免肿瘤特异性CD 8（+）细胞毒性T淋巴细胞对肿瘤细胞的识别。本文综述了不同组织学类型的人类肿瘤中MHC I类异常的潜在分子机制，这也可能对基于T细胞的免疫疗法的设计产生影响。
Tumor immune escape plays a critical role in cancer, but the mechanisms involved in this process have still to be defined. In the recent years, progress has been made in understanding how peptides presented by MHC class I molecules were generated, in particular which proteases are involved in this process and how intracellular pathways influence antigen presentation in professional antigen-presenting cells and in various types of malignancies. Different MHC class I abnormalities have been found in solid tumors of distinct origin, but also in hematopoietic diseases. These include structural alterations such as total, haplotype and allelic loss of the MHC class I heavy chain, deletions and point mutations, in particular in beta(2)-microglobulin and TAP1 as well as dysregulation of various components of the MHC class I antigen processing machinery (APM), which could occur at the epigenetic, transcriptional and posttranscriptional level. The lack or downmodulation of the expression of single or multiple components of the MHC class I antigen processing pathway may avoid the recognition of tumor cells by tumor-specific CD8(+) cytotoxic T lymphocytes. This review will give an overview of the underlying molecular mechanisms of MHC class I abnormalities in human tumors of distinct histology, which also might have an impact on the design of T cell-based immunotherapies.