Carretero Rafael, Romero José M, Ruiz-Cabello Francisco, Maleno Isabel, Rodriguez Felix, Camacho Francisco M, Real Luis M, Garrido Federico, Cabrera Teresa
Departamento de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Avd. Fuerzas Armadas 2, 18014 Granada, Spain.
Immunogenetics. 2008 Aug;60(8):439-47. doi: 10.1007/s00251-008-0303-5. Epub 2008 Jun 11.
Despite the potential efficacy of cancer immunotherapy in preclinical studies, it did not show yet significant positive clinical results in humans with only a small number of cancer patients demonstrating objective tumor regression. This poor clinical outcome can be explained by the generation of sophisticated tumor immune escape mechanism, in particular, abnormalities in the expression of HLA class I antigens. We have studied the expression of HLA class I antigens in ten metastatic lesions obtained from a melanoma patient undergoing immunotherapy. Five lesions were obtained after Interferon-alpha-2b treatment and five after autologous vaccination plus BCG (M-VAX). Eight metastases were regressing after immunotherapy while two were progressing. The eight regressing metastases showed high level of HLA class I expression, whereas the two progressing lesions had low levels as measured by real time PCR and immunohistological techniques. These results indicate a strong association between HLA class I expression and progression or regression of the metastatic lesions. Our data support the hypothesis that the level of HLA class I expression is an important parameter of tumor immune escape that needs to be monitored.
尽管癌症免疫疗法在临床前研究中具有潜在疗效，但在人类身上尚未显示出显著的积极临床结果，仅有少数癌症患者出现客观肿瘤消退。这种不佳的临床结果可归因于复杂的肿瘤免疫逃逸机制的产生，特别是HLA I类抗原表达异常。我们研究了一名接受免疫治疗的黑色素瘤患者的十个转移病灶中HLA I类抗原的表达情况。五个病灶是在α-干扰素-2b治疗后获得的，另外五个是在自体疫苗接种加卡介苗（M-VAX）后获得的。免疫治疗后八个转移灶在消退，而两个在进展。通过实时PCR和免疫组织学技术检测发现，八个消退的转移灶显示出高水平的HLA I类表达，而两个进展性病灶的水平较低。这些结果表明HLA I类表达与转移病灶的进展或消退之间存在密切关联。我们的数据支持这样的假设，即HLA I类表达水平是肿瘤免疫逃逸的一个重要参数，需要进行监测。
