Dutta Nirmal, Majumder Durjoy, Gupta Arnab, Mazumder Debendra Nath Guha, Banerjee Subrata
Biophysics Division, Cancer Centre Welfare Home and Research Institute, Thakurpukur, Kolkata, India.
Hum Immunol. 2005 Feb;66(2):164-9. doi: 10.1016/j.humimm.2004.10.010.
Malignant cells have been reported to escape immune surveillance by modulation of human lymphocyte antigen (HLA) class Ia molecule and/or other accessory molecules like TAP (transporter associated with antigen processing) and beta2-M expression. Most of these reports, however, are based on immunohistochemistry techniques with polymorphic- or isotype-specific antibodies. In the present study, we have instead used a locus-specific reverse transcriptase-polymerase chain reaction-based approach to detect the transcriptional expression of HLA class Ia as well as accessory molecules in gastric cancer. Our results indicate that HLA class Ia transcript is totally absent in only approximately 9% of cancer cases. Locus-specific expression of HLA-A and -B could, however, be detected in approximately 54% cases, whereas HLA-C was expressed in most of the cancer tissues. Interestingly, in some cases where HLA class Ia expression was observed, TAP1 expression could not be detected. Furthermore, we also investigated the frequency of nonclassical or HLA class Ib expression for molecules such as HLA-E and -G. HLA-G transcript was absent in gastric tissues both in cancerous and autologous normal region, whereas HLA-E was observed in a number of gastric cancers. Altogether these selective locus-specific losses of HLA class I along with impaired expression of accessory molecules may explain the complex phenomena by which gastric tumors escape both cytotoxic T-lymphocyte- as well as natural killer cell-mediated immune defense.
据报道,恶性细胞可通过调节人类淋巴细胞抗原(HLA)I类分子和/或其他辅助分子(如与抗原加工相关的转运体(TAP)和β2-微球蛋白(β2-M)的表达)来逃避免疫监视。然而,这些报道大多基于使用多态性或同型特异性抗体的免疫组织化学技术。在本研究中,我们转而采用基于位点特异性逆转录酶-聚合酶链反应的方法来检测胃癌中HLA I类以及辅助分子的转录表达。我们的结果表明,仅约9%的癌症病例中完全不存在HLA I类转录本。然而,在约54%的病例中可检测到HLA-A和-B的位点特异性表达,而大多数癌组织中都有HLA-C的表达。有趣的是,在一些观察到HLA I类表达的病例中,无法检测到TAP1的表达。此外,我们还研究了HLA-E和-G等分子的非经典或HLA Ib类表达频率。癌组织和自身正常区域的胃组织中均未检测到HLA-G转录本,而在许多胃癌中观察到了HLA-E的表达。总之,这些HLA I类的选择性位点特异性缺失以及辅助分子表达受损,可能解释了胃肿瘤逃避细胞毒性T淋巴细胞和自然杀伤细胞介导的免疫防御这一复杂现象。