Gastl G, Ebert T, Finstad C L, Sheinfeld J, Gomahr A, Aulitzky W, Bander N H
Department of Urology, New York Hospital-Cornell Medical Center, New York 10021, USA.
J Urol. 1996 Jan;155(1):361-7.
To determine the expression of MHC class I and II in human renal cancer.
We analyzed tissue sections from 22 primary and 28 metastatic renal cell carcinomas (RCC), as well as 31 established RCC cell lines. Tissue specimens from normal kidney and cell cultures of normal kidney epithelium were also studied. In addition, MHC antigen expression on RCC cell lines was assessed both before and after incubation with human recombinant interferon gamma (IFN-gamma). Antigen expression was determined by mixed hemadsorption, indirect immunofluorescence, fluorescence activated cell sorting (FACS) or immunoperoxidase staining using the monoclonal antibodies (mAbs) W6/32 (anti-MHC class I), mAbs NAMB-1 and BBM.1 (anti-beta-2 microglobulin), and mAbs L243 and 13-17 (anti-MHC class II) antibodies. Soluble beta-2 microglobulin in conditioned medium was measured by ELISA.
Normal renal epithelial cells, both in vivo and in vitro, showed low level expression of class I antigens. Immunohistochemical staining for MHC class II was limited to some proximal tubular cells, while cultured renal tubular cells were uniformly class II negative. The tumor cell populations in all 22 primary and in 26 of 28 (93%) metastatic RC specimens consisted predominantly of class I positive cells. Half of the samples from primary and metastatic tumors were class II negative. Incubation of RCC cell lines with IFN-gamma enhanced the expression of MHC class I, beta-2 microglobulin and class II. The upregulation of MHC expression was time and dose dependent and associated with increased release of soluble beta-2 microglobulin.
(i) Like normal kidney, virtually all primary human renal cell carcinomas express MHC class I antigens and retain this phenotype even during tumor progression and metastasis; (ii) class II expression on normal and RCC cells appears more limited but occurs frequently in both primary and metastatic lesions; and (iii) in most continuous RCC cell lines expression of MHC class I and II can effectively be stimulated by IFN-gamma. Since expression of MHC molecules might determine the immunogenicity of human RCC, its constitutive expression and augmentation could play an important role for the immunotherapy and prognosis of human renal cancer.
确定MHC I类和II类分子在人肾癌中的表达情况。
我们分析了22例原发性和28例转移性肾细胞癌（RCC）的组织切片，以及31株已建立的RCC细胞系。同时也研究了正常肾组织标本和正常肾上皮细胞培养物。此外，在用人重组干扰素γ（IFN-γ）孵育前后，评估RCC细胞系上的MHC抗原表达。使用单克隆抗体（mAb）W6/32（抗MHC I类）、mAb NAMB-1和BBM.1（抗β2微球蛋白）以及mAb L243和13-17（抗MHC II类）抗体，通过混合血细胞吸附、间接免疫荧光、荧光激活细胞分选（FACS）或免疫过氧化物酶染色来确定抗原表达。通过ELISA检测条件培养基中的可溶性β2微球蛋白。
正常肾上皮细胞在体内和体外均显示I类抗原低水平表达。MHC II类的免疫组化染色仅限于一些近端肾小管细胞，而培养的肾小管细胞均为II类阴性。在所有22例原发性和28例转移性RCC标本中的26例（93%）中，肿瘤细胞群体主要由I类阳性细胞组成。原发性和转移性肿瘤的一半样本为II类阴性。用IFN-γ孵育RCC细胞系可增强MHC I类、β2微球蛋白和II类的表达。MHC表达的上调具有时间和剂量依赖性，并与可溶性β2微球蛋白释放增加相关。
（i）与正常肾脏一样，几乎所有原发性人肾细胞癌均表达MHC I类抗原，即使在肿瘤进展和转移过程中仍保留此表型；（ii）正常和RCC细胞上的II类表达似乎更有限，但在原发性和转移性病变中均经常出现；（iii）在大多数连续的RCC细胞系中，MHC I类和II类的表达可被IFN-γ有效刺激。由于MHC分子的表达可能决定人RCC的免疫原性，其组成性表达和增强可能在人肾癌的免疫治疗和预后中起重要作用。
