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T-cell Unresponsiveness in Renal Cell Carcinoma Patients

  • Chapter
Clinical Management of Renal Tumors

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Abstract

There is evidence that immune responses to renal cell carcinoma do occur and in limited cases mediate tumor regression. This notion is supported by the infrequent though detectable occurrences of spontaneous regression in renal cell carcinoma (RCC) patients1 and by the higher incidence of renal cell tumors in patients that are immuno-suppressed after receiving kidney allografts.2–4 There is also a significant infiltrate of T lymphocytes in many primary renal tumors,5 and in some patients tumor-specific T-cell lines and clones have been expanded from their tumors.6–8 Furthermore, clonal expansion of T-cell receptor (TCR)α/β T cells has been reported in renal cell tumors, most notably in those that are regressing.9,10 More recently, a number of tumor-associated antigens were found to be expressed on RCC; among these are antigens shared by other tumor types, such as RAGE-1, Mage-3/-6, EphA2, Muc-1, and Her-2/neu, but also several that may be unique to RCC.11–17 Despite the potential for an effective immune response to RCC, it is not well developed in this patient population even after implement of various forms of immunotherapy designed to stimulate tumor immunity. The presence of an ineffective immune response is likely attributable to suppression induced by the developing tumor.

Recently a paradigm shift has occurred in treatment of metastatic RCC with the demonstration that small molecule inhibitors of receptor tyrosine kinases and antibodies that antagonize vascular endothelial growth factor (VEGF)/platelet-derived growth factor (PDGF) receptor signaling significantly increased not only the frequency of clinical responses but also their duration.18 While these targeted therapies are a significant improvement in the treatment of metastatic disease, they are not typically curative. To further improve the outcome for RCC patients’ future therapies will likely include combining the VEGF antagonist with strategies that promote antitumor immune responses. Thus, understanding how the tumor microenvironment can hinder the development of effective T-cell response to RCC remains an important issue to address. Here we describe the major suppressive pathways reported in RCC patients and provide some insight into their mechanism of action.

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Authors and Affiliations

  1. Department of Immunology, Cleveland Clinic Foundation, Cleveland, OH

    James H. Finke PhD

  2. Glickman Urological and Kidney Institute, Cleveland Clinic Foundation, Cleveland, OH

    Mahesh Goel MD

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  1. James H. Finke PhD
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  2. Mahesh Goel MD
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Editors and Affiliations

  1. Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, OH

    Ronald M. Bukowski MD

  2. Glickman Urological and Kidney Institute, Cleveland Clinic Foundation, Cleveland, OH

    Andrew C. Novick MD

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Finke, J.H., Goel, M. (2008). T-cell Unresponsiveness in Renal Cell Carcinoma Patients. In: Bukowski, R.M., Novick, A.C. (eds) Clinical Management of Renal Tumors. Humana Press. https://doi.org/10.1007/978-1-60327-149-3_7

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  • DOI: https://doi.org/10.1007/978-1-60327-149-3_7

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