The tumour suppressor gene CEACAM1 is completely but reversibly downregulated in renal cell carcinoma.
CEACAM1 acts as a tumour suppressor in various epithelial tumours. On the other hand, de novo expression of CEACAM1 is strongly associated with reduced disease-free survival of melanoma and non-small cell lung carcinoma patients. Since effector functions of natural killer and T cells are inhibited by homophilic CEACAM1 interaction, immune escape could be responsible for the poor prognosis of these patients. Here, we describe CEACAM1 expression in normal kidney, renal adenomas and renal cell carcinomas (RCC) using a novel antibody generated by genetic immunization. In normal kidney, CEACAM1 was found in epithelial cells of proximal tubules and in endothelial cells. In contrast, tumour cells of 30 clear cell, three chromophobic, and two chromophilic RCCs were completely devoid of CEACAM1. Renal adenomas also lacked CEACAM1 expression. Similarly, RCC cell lines CaKi1, CaKi2, A498, and RCC26 exhibited no or low-level CEACAM1 expression. However, CEACAM1 expression was transiently induced in A498 cells upon contact with allogeneic CD8+ T cells, mediated at least in part by interferon-gamma. Furthermore, the majority of tumour-infiltrating T and NK cells expressed CEACAM1 upon stimulation. Thus, transient expression of the tumour suppressor CEACAM1 by tumour cells and subsequent homophilic interaction with CEACAM1 on tumour-infiltrating lymphocytes could represent a novel immune escape mechanism in RCC.
Tumour Immunology Laboratory, Department of Urology, University Clinic Grosshadern, Ludwig-Maximilians University München, Munich, Germany.
Robert
R
Kammerer
Rainer
R
Riesenberg
Christoph
C
Weiler
Jens
J
Lohrmann
Julia
J
Schleypen
Wolfgang
W
Zimmermann
D000236:Adenoma / Q000235:genetics; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D015703:Antigens, CD / Q000235:genetics* / Q000276:immunology; D000943:Antigens, Differentiation / Q000235:genetics* / Q000276:immunology; D002272:Carcinoembryonic Antigen / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000235:genetics; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000235:genetics; D042783:Endothelial Cells / Q000502:physiology; D004847:Epithelial Cells / Q000502:physiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007372:Interferons / Q000235:genetics; D007680:Kidney Neoplasms / Q000235:genetics*; D007687:Kidney Tubules, Proximal / Q000503:physiopathology; D007694:Killer Cells, Natural / Q000502:physiology; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000502:physiology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; C069847:CD66 antigens; D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules; D007372:Interferons