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Updated: Jul 18, 2026
A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Immune escape for renal cell carcinoma: CD70 mediates apoptosis in lymphocytes
Julia Diegmann1, Kerstin Junker, Ivan F Loncarevic
1Core Unit Chip Application, Institute of Human Genetics and Anthropology, Friedrich Schiller University, Jena 07740, Germany.
Abstract:
Tumors can escape immune recognition and destruction through the induction of apoptosis in lymphocytes. Although renal cell carcinoma (RCC) is able to prevent immune recognition, only a few genes (such as FasL) that are relevant for RCC immune escape have been identified so far. We have previously shown that some apoptosis-inducing genes are overexpressed in RCC. We hypothesized that these genes could be part of the immune-escape strategy of these tumors. Here we report that CD70, a cytokine overexpressed in RCC, promotes lymphocyte apoptosis through interaction with its receptor CD27 and with the intracellular receptor-binding protein SIVA. Apoptosis increased after cocultivating lymphocytes with the RCC cell lines A498 and CAKI2. The addition of recombinant soluble CD70 to both native lymphocytes and a T-cell cell line resulted in increased lymphocyte apoptosis as well. Furthermore, induced apoptosis could be partially blocked with anti-CD27 and anti-CD70 antibodies. Our results strongly indicate a role for CD70 and CD27 receptor in lymphocyte apoptosis within the tumor environment. Apoptosis mediated by exposure to the CD70 secreted by tumor cells may contribute to the failure of RCC patients to develop an effective lymphocyte-mediated antitumor response.
Insights
Renal cell carcinoma (RCC) tumors can evade immune destruction by inducing lymphocyte apoptosis. Overexpressed CD70 in RCC promotes this apoptosis via CD27 interaction, hindering anti-tumor responses.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Tumors escape immune surveillance by inducing lymphocyte apoptosis.
- Renal cell carcinoma (RCC) exhibits immune escape mechanisms, with few identified genes like FasL involved.
- Previous studies indicated overexpression of apoptosis-inducing genes in RCC.
Purpose of the Study:
- To investigate the role of CD70 in RCC-mediated immune escape.
- To determine if CD70 overexpression contributes to lymphocyte apoptosis in RCC.
- To elucidate the molecular interactions involved in CD70-induced apoptosis.
Main Methods:
- Coculturing lymphocytes with RCC cell lines (A498 and CAKI2).
- Adding recombinant soluble CD70 to lymphocytes and T-cell lines.
- Utilizing anti-CD27 and anti-CD70 antibodies to block apoptosis.
Main Results:
- Lymphocyte apoptosis increased upon coculture with RCC cell lines.
- Recombinant soluble CD70 significantly enhanced lymphocyte apoptosis.
- Anti-CD27 and anti-CD70 antibodies partially inhibited the induced apoptosis.
- CD70 overexpression in RCC promotes lymphocyte apoptosis.
Conclusions:
- CD70 and its receptor CD27 play a crucial role in lymphocyte apoptosis within the tumor microenvironment.
- Tumor-secreted CD70 contributes to immune evasion in RCC by inducing apoptosis.
- This mechanism may impair effective lymphocyte-mediated anti-tumor responses in RCC patients.
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