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. 2006 Nov;8(11):933-8.
doi: 10.1593/neo.06451.

Immune escape for renal cell carcinoma: CD70 mediates apoptosis in lymphocytes

Julia Diegmann  1 , Kerstin Junker, Ivan F Loncarevic, Susanne Michel, Bettina Schimmel, Ferdinand von Eggeling
Affiliations

Immune escape for renal cell carcinoma: CD70 mediates apoptosis in lymphocytes

Julia Diegmann et al. Neoplasia. 2006 Nov.

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.

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Figures

Figure 1
Figure 1
Immunostaining for CD70, CD27, and SIVA on adherent growing cell lines. (A.1) Cell line A498 stained against CD70 (original magnification, x200). (A.2) Cell line A498 stained against CD27 (original magnification, x200). (A.3) Cell line A498 stained against SIVA (original magnification, x300). (B.1) Cell line CAKI1 stained against CD70 (original magnification, x200). (B.2) Cell line CAKI1 stained against CD27 (original magnification, x200). (B.3) Cell line CAKI1 stained against SIVA (original magnification, x300). (C.1) Cell line CAKI2 stained against CD70 (original magnification, x200). (C.2) Cell line CAKI2 stained against CD27 (original magnification, x200). (C.3) Cell line CAKI1 stained against SIVA (original magnification, x300).
Figure 2
Figure 2
Apoptosis ratios of T cells cocultured with RCC cell lines CAKI1 (left), CAKI2 (middle), and A498 (right). Caspase activity ratios are shown relative to normal caspase activity in MOLT-4 cells in culture. Vertical stripes: no antibody added; white: anti-CD70 antibody added; gray: anti-CD27 antibody added; black: isotype control added.
Figure 3
Figure 3
Effect of recombinant soluble CD70 and anti-CD70 and anti-CD27 antibodies on the apoptosis rate of MOLT4 cells (left) and native lymphocytes (right). Rmscd70 was added at a concentration of 50 ng/ml. Vertical stripes: no antibody added; white: anti-CD70 antibody added; gray: anti-CD27 antibody added; black: isotype control added.
Figure 4
Figure 4
Schematic representation of apoptosis induction through CD70 expression in RCC cells. (A) Apoptosis induction through cell-cell contact. CD27 receptor is expressed by lymphocytes, and CD70 ligand is membrane-bound in RCC cells. Apoptosis is induced after the binding of death-domain substitute SIVA, which initiates caspase activation. (B) Apoptosis induction without cell-cell contact. Membrane-bound CD70 ligand is cleaved and binds to the CD27 receptor. Apoptosis is induced after the binding of death-domain substitute SIVA, which initiates caspase activation.
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References

    1. Finke J, Ferrone S, Frey A, Mufson A, Ochoa A. Where have all the T cells gone? Mechanisms of immune evasion by tumors. Immunol Today. 1999;20:158–160. - PubMed
    1. Uzzo RG, Rayman P, Rolenko V, Clark PE, Bloom T, Ward AM, Molto L, Tannenbaum C, Worford LJ, Bukowski R, et al. Mechanisms of apoptosis in T cells from patients with renal cell carcinoma. Clin Cancer Res. 1999;5:1219–1229. - PubMed
    1. Diegmann J, Junker K, Gerstmayer B, Bosio A, Hindermann W, Rosenhahn J, von Eggeling F. Identification of CD70 as a diagnostic biomarker for clear cell renal cell carcinoma by gene expression profiling, real-time RT-PCR and immunohistochemistry. Eur J Cancer. 2005;41:1794–1801. - PubMed
    1. Junker K, Hindermann W, von Eggeling F, Diegmann J, Haessler K, Schubert J. CD70: a new tumor specific biomarker for renal cell carcinoma. J Urol. 2005;173:2150–2153. - PubMed
    1. Diegmann J, Tomiuk S, Sanjmyatav J, Junker K, Hindermann W, von Eggeling Comparative transcriptional and functional profiling of clear cell and papillary renal cell carcinoma. Int J Mol Med. 2006;18:395–403. - PubMed

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