The tumour suppressor gene CEACAM1 is completely but reversibly downregulated in renal cell carcinoma
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Updated: Aug 9, 2026
Modeling Spontaneous Metastatic Renal Cell Carcinoma (mRCC) in Mice Following Nephrectomy
Published on: April 29, 2014
Robert Kammerer1, Rainer Riesenberg, Christoph Weiler
1Tumour Immunology Laboratory, Department of Urology, University Clinic Grosshadern, Ludwig-Maximilians University München, Munich, Germany.
Abstract:
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.
Insights
The tumor suppressor CEACAM1 is absent in renal cell carcinoma (RCC) cells, but its transient expression upon T cell contact may facilitate immune escape. This suggests a novel mechanism for poor prognosis in RCC patients.
Area of Science:
- Oncology
- Immunology
- Cell Biology
Background:
- CEACAM1 functions as a tumor suppressor in epithelial cancers.
- CEACAM1 expression correlates with poor survival in melanoma and non-small cell lung carcinoma.
- Homophilic CEACAM1 interactions can inhibit natural killer (NK) and T cell functions, suggesting immune evasion as a cause of poor prognosis.
Purpose of the Study:
- To investigate CEACAM1 expression in normal kidney, renal adenomas, and renal cell carcinomas (RCC).
- To explore the role of CEACAM1 in immune escape mechanisms within the tumor microenvironment of RCC.
Main Methods:
- Utilized a novel antibody generated by genetic immunization to detect CEACAM1 expression.
- Analyzed CEACAM1 levels in normal kidney tissues, renal adenomas, and various subtypes of RCC (clear cell, chromophobic, chromophilic).
- Examined CEACAM1 expression in RCC cell lines (CaKi1, CaKi2, A498, RCC26) and its induction upon co-culture with CD8+ T cells, including assessment of interferon-gamma mediation.
Main Results:
- CEACAM1 was detected in epithelial cells of proximal tubules and endothelial cells of normal kidney.
- Tumor cells in all analyzed RCC subtypes and renal adenomas were completely devoid of CEACAM1 expression.
- RCC cell lines showed minimal to no CEACAM1 expression, but it was transiently induced in A498 cells upon interaction with CD8+ T cells, partly via interferon-gamma.
- Tumor-infiltrating T and NK cells expressed CEACAM1 following stimulation.
Conclusions:
- Absence of CEACAM1 in renal cell carcinoma and adenoma cells is a key finding.
- Transient CEACAM1 expression by tumor cells upon immune cell contact, and subsequent homophilic interaction with CEACAM1 on tumor-infiltrating lymphocytes, represents a potential novel immune escape mechanism in RCC.
- This mechanism may contribute to the poor prognosis observed in certain RCC patients.
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