Immune Checkpoint Inhibitors in the Treatment of Renal Cancer: Current State and Future Perspective

International Journal of Molecular Sciences

Elisa Pellegrini¹  Laura Doni¹  Daniele Lavacchi¹  Marco Carini¹  Fabrizio Di Maida¹  Serena Pillozzi¹  ValeriaEmma Palmieri¹  MarinellaMicol Mela¹  Lorenzo Antonuzzo¹  Amedeo Amedei² 

[1]Clinical Oncology Unit, AOU Careggi, 50134 Firenze, Italy

[2]Department of Experimental and Clinical Medicine, University of Firenze, 50134 Firenze, Italy

关键词: immune checkpoint inhibitors;    renal cell carcinoma;    tyrosine kinase inhibitors;    predictive biomarkers;   

DOI  :  10.3390/ijms21134691

来源: DOAJ

【 摘 要 】

Systemic treatment of renal cancer (RCC) has undergone remarkable changes over the past 20 years with the introduction of immunotherapeutic agents targeting programmed cell death (PD-1)/programmed death-ligand 1 (PD-L1) axis, as a single-agent or combined with anti-CTLA-4 monoclonal antibodies (MoAbs) or a multi-target vascular endothelial growth factor-(VEGF) tyrosine kinase inhibitor (TKI). In this paper, we review the main evidence on the use of Immune Checkpoint Inhibitors (ICIs) for RCC treatment from the first demonstration of activity of a nivolumab single agent in a phase I trial to the novel combination strategies (anti-PD-1 plus anti-CTLA4 or anti-PD-1 plus TKI). In addition, we discuss the use of anti-PD-1/PD-L1 agents in patients with non-clear cells and rare histological subtype RCC. Then, we critically examine the current findings in biomarkers that have been proposed to be prognostic or predictive to the response of immunotherapy including immune gene expression signature, B7-H1 expression, PBRM1 loss of function, PD-L1 expression, frame shift indel count, mutations in bromodomain-containing genes in patients with MiT family translocation RCC (tRCC), high expression of the T-effector gene signature, and a high myeloid inflammation gene expression pattern. To date, a single biomarker as a predictor of response has not been established. Since the dynamic behavior of the immune response and the different impact of ICI treatment on patients with specific RCC subtypes, the integration of multiple biomarkers and further validation in clinical trials are needed.

【 授权许可】

Unknown