Cordon-Cardo C, Fuks Z, Drobnjak M, Moreno C, Eisenbach L, Feldman M
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Cancer Res. 1991 Dec 1;51(23 Pt 1):6372-80.
The expression of monomorphic determinants of the histocompatibility leukocyte antigens (HLA) class I antigens by human malignant tumor cells was studied in tissue specimens of 70 primary tumor lesions obtained from patients with carcinoma of the breast (41 patients), colon (8 patients), urinary bladder (8 patients), and kidney (13 patients), and in samples of either synchronous or metachronous lymph node, lung, or liver metastases available in 44 of the patients. The frequencies of HLA class I expressor and nonexpressor tumor cells were determined by immunohistochemical staining of histological sections of fresh frozen tissue samples with the W6/32 monoclonal antibody. The tumor cell populations in the majority of the primary lesions consisted predominantly of HLA-immunoreactive cells (observed in 38 of 70 patients; 54%), especially in those patients who did not have clinical evidence of metastatic disease (8 of 11 patients; 73%). Various degrees of loss of reactivity were observed in other primary lesions, although in only 8 (12%) tumors (7 of which were obtained from patients with metastatic disease), the neoplastic cells were nearly exclusively HLA-nonreactive. In contrast, the majority of metastatic lesions consisted of either predominantly HLA-negative cells (33 of 44 specimens; 75%) or mixed populations (10 of 44 specimens; 23%), whereas only one metastatic lesion manifested HLA class I antigen staining in more than 70% of its tumor cells (P = 0.0005). Intravascular clusters of tumor cells consisted predominantly of HLA class I nonexpressors. The observed patterns of distribution of HLA expressors and nonexpressor tumor cells are compatible with the notion that HLA-negative cells in human carcinomas manifest a selective advantage with regard to metastatic progression and growth. The suppressed expression of major histocompatibility complex class I antigens on metastatic cells may lead to failure of presentation of cell surface tumor specific epitopes to host cytotoxic T-lymphocytes. Such a process would enable tumor cells to evade host immune responses and would promote and enhance cell dissemination and metastatic growth.
在取自70例原发性肿瘤病变组织标本中，研究了人类恶性肿瘤细胞组织相容性白细胞抗原（HLA）I类抗原单态决定簇的表达情况。这些标本来自乳腺癌患者（41例）、结肠癌患者（8例）、膀胱癌患者（8例）和肾癌患者（13例），并且还研究了44例患者的同步或异时性淋巴结、肺或肝转移灶样本。通过用W6/32单克隆抗体对新鲜冷冻组织样本的组织切片进行免疫组织化学染色，确定了HLA I类表达和不表达肿瘤细胞的频率。大多数原发性病变中的肿瘤细胞群体主要由HLA免疫反应性细胞组成（70例患者中有38例观察到；54%），特别是在那些没有转移疾病临床证据的患者中（11例患者中有8例；73%）。在其他原发性病变中观察到不同程度的反应性丧失，尽管仅在8例（12%）肿瘤中（其中7例取自转移性疾病患者），肿瘤细胞几乎完全不具有HLA反应性。相比之下，大多数转移灶主要由HLA阴性细胞组成（44个标本中有33个；75%）或混合群体（44个标本中有10个；23%），而只有一个转移灶在其70%以上的肿瘤细胞中表现出HLA I类抗原染色（P = 0.0005）。肿瘤细胞的血管内簇主要由HLA I类不表达细胞组成。观察到的HLA表达和不表达肿瘤细胞的分布模式与以下观点一致，即人类癌症中的HLA阴性细胞在转移进展和生长方面表现出选择性优势。转移性细胞上主要组织相容性复合体I类抗原的表达受抑制可能导致细胞表面肿瘤特异性表位无法呈递给宿主细胞毒性T淋巴细胞。这样一个过程将使肿瘤细胞逃避宿主免疫反应，并促进和增强细胞播散和转移生长。
