LOSS OF HLA CLASS-I EXPRESSION IN PROSTATE-CANCER - IMPLICATIONS FOR IMMUNOTHERAPY
LOSS OF HLA CLASS-I EXPRESSION IN PROSTATE-CANCER - IMPLICATIONS FOR IMMUNOTHERAPY
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DOI：
10.1016/s0090-4295(99)80301-x
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发表时间：
1995-11-01
期刊：
影响因子：
2.1
通讯作者：
STERN, PL
中科院分区：
文献类型：
--
作者：
BLADES, RA;KEATING, PJ;STERN, PL
目标。目前还没有可靠的预测个体患者的明显局限性前列腺癌的转移潜力或对晚期疾病患者的满意治疗。可能会影响肿瘤恶化的因素之一是细胞的免疫反应,和中央这是人类白细胞抗原(HLA)系统,以起到限制t细胞识别潜在的肿瘤抗原,据报道在一些癌症下来调节HLA类我表达的肿瘤细胞与不良预后有关,在这个报告中,HLA I型和II类表达式进行了调查在良性和恶性前列腺疾病,首先确定HLA表达改变的程度，其次评估HLA表达是否与疾病进展有关。HLA表达通过免疫组织化学评估，利用一组单克隆抗体识别单态决定因子和普通HLA I类等位基因产物。与良性组织中正常的HLA I类表达相比，在34%的原发性前列腺癌和80%的淋巴结转移中，HLA I类表达完全丧失。当评估个体等位基因表达时，原发性前列腺癌中下调的最小估计为85%，转移性前列腺癌中下调的最小估计为100%。这项研究表明，与其他肿瘤相比，前列腺癌的HLA I类丢失率更高，这表明免疫系统可能在前列腺癌的进展中发挥重要作用，并对晚期疾病免疫治疗方案的设计和成功具有重要意义。
Objectives. There is currently no reliable predictor of the metastatic potential of apparently localized prostate cancer in an individual patient or satisfactory treatment for patients with advanced disease. One of the factors that may influence tumor progression is the cellular arm of the immune response, and central to this is the human leukocyte antigen (HLA) system, which acts to restrict T-cell recognition of potential tumor antigens, It has been reported in some cancers that down regulation of HLA class I expression by the tumor cells is associated with poor prognosis, In this report, HLA class I and II expression have been investigated in both benign and malignant prostate disease, first to define the extent of altered HLA expression and second to assess whether HLA expression may be related to disease progression.Methods. HLA expression was assessed by immunohistochemistry utilizing a set of monoclonal antibodies that recognize both monomorphic determinants and the commoner HLA class I allelic products.Results. in contrast to the normal HLA class I expression of the benign tissue, complete loss of HLA class I expression occurred in 34% of primary prostate cancers and 80% of lymph node metastases. When individual allelic expression was assessed, the minimum estimate of down regulation was 85% in the primary prostate cancers and 100% of the metastases.Conclusions. This investigation has demonstrated a higher rate of HLA class I loss than has been reported in other tumors and would suggest that the immune system may have an important role in the progression of prostate cancer, as well as having implications for the design and success of immunotherapy regimens in advanced disease.