Is immunotherapy re-entering the kidney cancer arena from the back door? Considerations from the Phase I/II study of siltuximab

Evaluation of: Rossi JF, Negrier S, James ND et al.: A Phase I/II study of siltuximab (CNTO 328), an anti-interleukin-6 monoclonal antibody, in metastatic renal cell cancer. Br. J. Cancer 103, 1154-1162 (2010). For years, immunotherapy was the mainstay of treatment for advanced kidney cancer. The recent development of molecularly targeted agents, and of antiangiogenic agents in particular, has completely changed this scenario, leaving immunotherapy with a minor role in treatment, if any. Recent insights in the mechanisms of resistance to these drugs suggest that the immune system could play a relevant role. In particular, IL-6 appears to cooperate with other growth factors in the recruitment of bone marrow-derived immune cells, ultimately leading to resistance to antiangiogenic agents. Furthermore, it is now clear that monoclonal antibodies actively interact with the immune system and show significant immune-modulating effects per se. Further translation research on this issue is much needed.