Major histocompatibility complex class I and class II expression in renal cell carcinoma and modulation by interferon gamma Journal Article


Authors: Gastl, G.; Ebert, T.; Finstad, C. L.; Sheinfeld, J.; Gomahr, A.; Aulitzky, W.; Bander, N. H.
Article Title: Major histocompatibility complex class I and class II expression in renal cell carcinoma and modulation by interferon gamma
Abstract: Purpose: To determine the expression of MHC class I and II in human renal canc Materials and Methods: 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 (FAGS) 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. Results: 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. Conclusions: (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.
Keywords: antigen expression; gene; kidney neoplasms; major histocompatibility complex; monoclonal-antibodies; specificity; rejection; melanoma-cells; determinants; interferon type ii; surface-antigens; cancer; beta 2-microglobulin; lymphokine
Journal Title: Journal of Urology
Volume: 155
Issue: 1
ISSN: 0022-5347
Publisher: Elsevier Science, Inc.  
Date Published: 1996-01-01
Start Page: 361
End Page: 367
Language: English
ACCESSION: WOS:A1996TJ43400139
DOI: 10.1016/s0022-5347(01)66661-8
PROVIDER: wos
PUBMED: 7490887
Notes: Article -- Source: Wos
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  1. Joel Sheinfeld
    254 Sheinfeld
  2. Connie L. Finstad
    45 Finstad