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Immunologic mechanisms in RCC and allogeneic renal transplant rejection

Nature Reviews Urology volume 7, pages 339–347 (2010)Cite this article

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Abstract

The tolerance state that exists between renal cell carcinoma (RCC) and the host's immune system would be an ideal situation in the setting of human kidney transplantation, in which graft tolerance is the ultimate goal of immunosuppressive therapy. On the other hand, acute rejection, as it appears in renal allografts, would be the optimal immunologic situation in patients with RCC. Analysis of the underlying mechanisms of acute allograft rejection and local pro-tumor immunosuppression could help to identify potential therapeutic targets for inducing immune tolerance in allograft recipients and immune rejection in RCC patients. Experimental kidney transplantation might be a suitable model in which to analyze these processes. Macrophages are a prominent and vital cell type in the cellular infiltrate seen in both RCC and renal allografts. Depending on their polarization, they can initiate and promote either proinflammatory or pro-tumor responses, which lead to tissue rejection or acceptance, respectively. Improved understanding of macrophage biology could lead to therapeutic modification of their function in order to promote a desirable immunologic response in either RCC or transplant tissue.

Key Points

  • Renal cell carcinoma (RCC) is an immunoresponsive tumor, for which emerging, immune-based treatments are being tested in clinical studies

  • The immunosuppressive tumor microenvironment inhibits an effective immune response by inducing functional anergy of local macrophages and T cells

  • Acute renal allograft rejection is a useful model in which to study the inflammatory and immune mechanisms required to induce tumor rejection

  • Macrophages show a functional plasticity, displaying either an M1 (proinflammatory) or M2 (immunosuppressive and pro-tumor) phenotype

  • Potential therapeutic strategies that target macrophages include the induction of macrophage depletion or reprogramming, and interference with macrophage-mediated co-stimulation of T cells

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Figure 1: Both clear cell renal cell carcinoma (RCC) and human renal allograft show a strong mononuclear cell infiltrate of lymphocytes and monocytes/macrophages.
Figure 2: Schematic representation of the plasticity of macrophages.
Figure 3: Tissue-specific recruitment of monocytes.
Figure 4: Co-stimulatory signals provided by macrophages to naive T cells.

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Acknowledgements

A. Stenzl was supported by a grant from the Deutsche Forschungsgemeinschaft (DFG, SFB 685 C5). The authors thank Hermann-Josef Gröne, Department of Cellular and Molecular Pathology, German Cancer Research Center, Heidelberg, Germany, and Hans-Georg Rammensee, Department of Immunology, University of Tübingen, Germany for their careful reading of this manuscript and for their thoughtful comments. The authors additionally thank Hermann-Josef Gröne for providing the photomicrographs.

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    Jens Bedke & Arnulf Stenzl

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Bedke, J., Stenzl, A. Immunologic mechanisms in RCC and allogeneic renal transplant rejection. Nat Rev Urol 7, 339–347 (2010). https://doi.org/10.1038/nrurol.2010.59

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