Immune Self-tuning in Renal Cell Carcinoma
Therapeutic Perspectives in the Era of Targeted Therapies
In recent years the development of new agents developed for targeting mTor or angiogenetic tyrosine kinases has substantially improved prognosis for patients with metastatic RCC.118 Nevertheless, immunotherapy is expected to experience a revival in the treatment of RCC: the growing knowledge concerning the molecular mechanisms that allow RCC to escape immune attack offers new therapeutic options, also in terms of the new targeted therapies. Furthermore, there are distinct immunological effects of targeted therapies, which have been only partially elucidated. Inhibitors of small molecules might enhance the immunogenicity of tumour cells by different mechanisms: making them more susceptible to killing by immune cells and by reversing the immune dysbalance induced by the tumour through direct action on immune cells or tumour cells (see Figure 2), or indirectly through reducing tumour burden.119–122
Therefore, sequencing or combining
targeted therapies with immunotherapeutic strategies – including both mechanisms of immune activation and disruption of immuno- suppressive pathways – may represent an attractive therapeutic concept. The efficacy of a standard immunotherapy combined with
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