Checkpoint inhibitor immunotherapy in kidney cancer.
Wenxin XuMichael B AtkinsDavid F McDermottPublished in: Nature reviews. Urology (2020)
Kidney cancer has unique features that make this malignancy attractive for therapeutic approaches that target components of the immune system. Immune checkpoint inhibition is a well-established part of kidney cancer treatment, and rapid advances continue to be made in this field. Initial preclinical studies that elucidated the biology of the programmed cell death 1 (PD-1), programmed cell death 1 ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) immune checkpoints led to a series of clinical trials that resulted in regulatory approval of nivolumab and the combination of ipilimumab plus nivolumab for the treatment of advanced renal cell carcinoma. Subsequent data led to approvals of combination strategies of immune checkpoint inhibition plus agents that target the vascular endothelial growth factor receptor and a shift in the current standard of renal cell carcinoma care. However, controversies remain regarding the optimal therapy selection and treatment strategy for individual patients, which might be eventually overcome by current intensive efforts in biomarker research. That work includes evaluation of tumour cell PD-L1 expression, gene expression signatures, CD8+ T cell density and others. In the future, further advances in the understanding of immune checkpoint biology might reveal new therapeutic targets beyond PD-1, PD-L1 and CTLA-4, as well as new combination approaches.
Keyphrases
- renal cell carcinoma
- vascular endothelial growth factor
- gene expression
- clinical trial
- papillary thyroid
- healthcare
- end stage renal disease
- cell therapy
- ejection fraction
- single cell
- squamous cell
- newly diagnosed
- dna methylation
- chronic kidney disease
- palliative care
- stem cells
- genome wide
- machine learning
- squamous cell carcinoma
- replacement therapy
- combination therapy
- prognostic factors
- cell cycle
- cell proliferation
- young adults
- childhood cancer
- current status
- artificial intelligence
- binding protein
- open label