Abstract
Renal cell carcinoma encompass distinct diseases with different pathologic features and distinct molecular pathways. Immune checkpoint inhibitors targeting the programmed death receptor ligand 1 (PD-L1)/programmed death receptor 1 (PD-1) pathway alone or in combination have greatly changed clinical management of metastatic renal cell carcinoma, now competing with antiangiogenic drugs in monotherapy for first-line treatment. However, long-term response rates are low, and biomarkers are needed to predict treatment response. Quantification of PD-L1 expression by immunohistochemistry was developed as a promising biomarker in clinical trials, but with many limitations (different antibodies, tumour heterogeneity, specimens, and different thresholds of positivity). Other biomarkers, including tumour mutational burden and molecular signatures, are also developed and discussed in this review.
Highlights
Renal cell carcinoma (RCC) represents 2% to 3% of all cancers, corresponding to 338,000 new cases diagnosed each year worldwide [1]
Patients with intermediate and poor risk according to the International Metastatic Database Consortium (IMDC) score benefitted the most from the association of ipilimumab and nivolumab with a median overall survival (OS) not reached with nivolumab plus ipilimumab versus 26 months with sunitinib (HR = 0.63; 99.8% CI, 0.44 to 0.89; p < 0.001)
Renal cell carcinoma encompasses distinct diseases and molecular alterations with clear cell renal cell carcinoma (ccRCC) the most frequent entity characterized by its angiogenesis and its immune micro-environment targeted by antiangiogenic drugs and immune checkpoint inhibitors (ICI)
Summary
Renal cell carcinoma (RCC) represents 2% to 3% of all cancers, corresponding to 338,000 new cases diagnosed each year worldwide [1]. The development of targeted therapies, including vascular endothelial growth factor (VEGF) pathway inhibitors, mammalian target of rapamycin (mTOR) inhibitors, and, more recently, the emergence of immune checkpoint inhibitors (ICI), such as anti-programmed death receptor 1 (PD-1), anti-programmed death receptor ligand 1 (PD-L1), and anti-cytotoxic T lymphocytes antigen 4 (CTLA-4), have led to a wide treatment landscape remodelling, targeting the tumour micro-environment (Table 1). There is a biological rationale to use them in association In this comprehensive review, we will discuss: (1) the histologic subtypes and the molecular pathways related, (2) the anti-tumour immune response and its interaction with angiogenesis, (3) the current landscape of targeted immunotherapy in RCC, and (4) the predictive biomarkers in RCC, including their limitations and the perspectives
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
