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Immunotherapeutic strategies in kidney cancer—when TKIs are not enough

Nature Reviews Clinical Oncology volume 6, pages 478–487 (2009)Cite this article

Abstract

FDA approval of the multitargeted, antiangiogenic tyrosine kinase inhibitors (TKIs) sunitinib and sorafenib, and the serine and threonine mammalian target of rapamycin inhibitor, temsirolimus, has revolutionized the management of metastatic clear-cell renal-cell carcinoma (CC-RCC). The inability of these targeted therapies to provide durable complete responses, however, is a serious limiting factor to their clinical usefulness. Although immunotherapeutic approaches in advanced disease are increasingly regarded as a historical treatment paradigm, we propose that a fundamental understanding of immunobiology in CC-RCC can improve the selection of patients for high-dose intravenous interleukin 2 and facilitate the development of novel immunotherapeutic strategies. In our opinion, immunotherapeutic strategies have an important place in the management of advanced CC-RCC in the era of biological targeted therapy.

Key Points

  • Tumor immunology is highly complex and is dependent on both tumor and host factors

  • High-dose interleukin 2 is the only therapy that can cure a minority of patients with metastatic clear-cell renal-cell carcinoma (CC-RCC); interferon alpha can also induce durable complete responses but in comparatively fewer patients

  • CC-RCC histopathology and carbonic anhydrase IX immunohistochemistry has the potential to optimize the selection of patients for high-dose interleukin 2 immunotherapy

  • Immunotherapies based on anti-tumor-associated-antigen strategies, such as vaccines, are currently undergoing clinical trials, but no agent has demonstrated survival benefit in metastatic CC-RCC

  • Disease response evaluation and the utility of RECIST (Response Evaluation Criteria In Solid Tumors) have to be formally re-assessed for immunotherapy trials

  • Translational studies within immunotherapy clinical trials will be vital to identify biomarkers of disease response and to develop a better overall understanding of tumor immunology

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Figure 1: Immunomodulatory factors in human tumor biology.
Figure 2: Vaccine strategies in solid tumors and their applications in metastatic CC-RCC (highlighted in red).
Figure 3: A proposed schematic for translational studies in future immunotherapy metastatic CC-RCC trials involving vaccines (V), cytokines (C), or adoptive T-cell therapy (ATT).
Figure 4: Potential strategies for overcoming immunosuppression in metastatic CC-RCC.

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  1. Freeman Hospital, Newcastle upon Tyne, UK

    Swethajit Biswas

  2. University of Cambridge, Cambridge, UK

    Tim Eisen

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S. Biswas declares no competing interests. T. Eisen is a Consultant for Bayer, Pfizer, Schering Plough and Wyeth; he is on the Speakers bureau for Bayer, Pfizer and Wyeth and receives grant/research support from Bayer, Pfizer and Schering Plough.

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Biswas, S., Eisen, T. Immunotherapeutic strategies in kidney cancer—when TKIs are not enough. Nat Rev Clin Oncol 6, 478–487 (2009). https://doi.org/10.1038/nrclinonc.2009.91

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