Bubeník Jan
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, 166 37 Prague 6, Czech Republic.
Oncol Rep. 2003 Nov-Dec;10(6):2005-8.
MHC class I downregulation is an important mechanism of tumour escape from T cell-mediated immune responses. Approximately 40-90% of human tumours derived from various MHC class I+ tissues were reported to be MHC class I deficient. Decreased or absent MHC class I expression is frequently associated with the invasive and metastatic tumour phenotype. Altered MHC class I antigen expression involves total loss, loss of haplotype, locus downregulation, allelic loss or downregulation, and combinations. Description of partial or complete losses of MHC class I molecules in tumour cells as mechanisms of immune escape often fails to consider an increased susceptibility to NK cell-mediated lysis, which is a direct consequence of such losses. A low MHC class I level favours NK cells as effectors, whereas a high level of MHC class I favours T cells as effectors. The microheterogeneity of MHC class I expression in tumour cell populations, the balance of the MHC-restricted and MHC-unrestricted defence as well as the selective pressure of antigen-specific (CTL) and antigen non-specific (NK) effector mechanisms decide the final outcome of the MHC class I expression in the primary tumour and its metastases as well as the final outcome of the tumour defence reaction. Despite the MHC class I molecule deficiency and the resulting absence of the CD8+ T cell-mediated immunity, the tumour hosts were found to be capable of being immunized against MHC class I- tumours. The purpose of this review is to discuss the positive results of MHC class I- tumour treatment obtained with immunomodulatory cytokines and tumour vaccines, as well as the prospects and limitations of such therapy.
MHC I类分子下调是肿瘤逃避T细胞介导的免疫反应的重要机制。据报道，源自各种MHC I类阳性组织的人类肿瘤中，约40-90%存在MHC I类缺陷。MHC I类分子表达降低或缺失常与肿瘤的侵袭性和转移表型相关。MHC I类抗原表达的改变包括完全缺失、单倍型缺失、基因座下调、等位基因缺失或下调以及多种情况的组合。将肿瘤细胞中MHC I类分子的部分或完全缺失描述为免疫逃逸机制时，往往没有考虑到由此导致的对NK细胞介导的细胞溶解敏感性增加，而这正是此类缺失的直接后果。低水平的MHC I类分子有利于NK细胞作为效应细胞，而高水平的MHC I类分子有利于T细胞作为效应细胞。肿瘤细胞群体中MHC I类分子表达的微异质性、MHC限制和非MHC限制防御的平衡以及抗原特异性（CTL）和抗原非特异性（NK）效应机制的选择压力，决定了原发性肿瘤及其转移灶中MHC I类分子表达的最终结果以及肿瘤防御反应的最终结果。尽管存在MHC I类分子缺陷以及由此导致的CD8+ T细胞介导的免疫缺失，但发现肿瘤宿主仍能够针对MHC I类阴性肿瘤进行免疫。本综述的目的是讨论使用免疫调节细胞因子和肿瘤疫苗治疗MHC I类阴性肿瘤所取得的积极成果，以及此类治疗的前景和局限性。
