Dear Colleagues,

Kidney cancer accounts for 403 000 new cases and 175 000 deaths per year worldwide. Renal cell carcinoma (RCC) represents around 90% of kidney cancers in adults. Approximately one-third of patients will have metastatic disease at the time of diagnosis and an additional 20% will ultimately develop metastatic disease. The recent development of immune-checkpoint inhibitors (ICIs) has revolutionized the therapeutic approaches of multiple types of cancer, including metastatic (mRCC). Immune checkpoints are key regulators of the immune system and protect the host from autoimmune responses. Immune checkpoints can also be expressed on the surface of tumor cells and promote an immunosuppressive microenvironment that supports tumor growth. The blockade of immune checkpoints restores the activation of the immune system towards tumor cells. Multiple ICIs have been approved by the FDA for RCC therapies, including monoclonal antibodies that target the cytotoxic T-lymphocyte-associated protein-4 (CTLA-A4) or the programmed death-1 (PD-1). These antibodies are efficient and safe as monotherapy, in combination with other ICIs or with anti-angiogenic therapeutic compounds (the therapeutic references for 15 years). Thus, therapies based on ICIs are now recommended as the first-line therapy in clear-cell cancers with the observation of long-lasting disease control. However there is still a lack of understanding of who will benefit from these therapies, and the development of predictive biomarkers of efficacy or adverse events are urgently needed. The duration of treatment, new therapeutic strategies and the therapeutic sequence for patients receiving ICI-based therapies, including the role of surgery, are also far from being well defined. There is also a need to develop therapeutic approaches for patients resistant to the first generation of ICIs, and to understand whether some quality attributes of therapeutic monoclonal antibodies might play a role in their efficacy or the development of adverse events. Consequently, complete remissions remain rare events. Overall, a new era evolved from the arrival of ICIs, but we are only at the beginning of this era. In this Special Issue, we are inviting research articles, reviews, as well as opinion papers supporting the understanding of ICIs’ mechanism of action, developing biomarkers of efficacy/resistance or biomarkers of adverse events, developing bioassays to assess the efficacy of ICIs, investigating the effect of therapeutic antibodies’ quality attributes on therapeutic efficacy or adverse events, as well as studies investigating the therapeutic sequence of ICIs and developing therapeutic approaches for patients with tumors resistant to ICIs. The scope is deliberately broad to allow contributions on diverse aspects of the topic.

Dr. Thierry Massfelder
Dr. Philippe Barthélémy
Dr. Valerian Dormoy
Dr. Mamatha Garige
Guest Editors

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• renal cell carcinoma
• immunotherapy
• immune checkpoints
• immune-checkpoint inhibitors
• biomarkers
• therapeutic monoclonal antibody
• quality attributes
• nephrectomy