Cytokine therapy for renal cell cancer: the evolving role of immunomodulation

Renal cell carcinoma (RCC) is a chemo-resistant malignancy. For many years the only treatment for advanced disease was immunotherapy; the cytokines IFN-α and IL-2 were widely used but offered limited objective response rates of 10–20% and only modest survival benefits in the majority of cases. The last decade has witnessed a marked increase in the availability of novel targeted therapies demonstrating anti-tumor activity and, more importantly, providing a meaningful impact on overall survival. However, to date, immunotherapy, in the form of high-dose IL-2, remains the only treatment modality able to induce durable complete remissions and/or cure in metastatic RCC, albeit in a small minority of patients. A priority for immunotherapy research should be to investigate strategies that may augment the effectiveness of immunomodulation and enable a greater proportion of patients with advanced RCC to benefit from this treatment. A number of approaches are discussed; combinations with molecularly targeted agents ...