Nature reviews. Urology
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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. ⋯ 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.
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Technical advances in the development of organoid systems enable cell lines, primary adult cells, or stem or progenitor cells to develop into diverse, multicellular entities, which can self-renew, self-organize, and differentiate. These 3D organoid cultures have proven to be of value in increasing our understanding of the biology of disease and offer the potential of regenerative and genetic therapies. The successful application of 3D organoids derived from adult tissue into urological cancer research can further our understanding of these diseases and could also provide preclinical cancer models to realize the precision medicine paradigm by therapeutic screening of individual patient samples ex vivo. ⋯ Organoid models can also improve our comprehension of aspects of particular diseases; for example, in prostate cancer, 3D organoids can aid in the identification of tumour-initiating cells from an epithelial cell lineage. Furthermore, kidney organoid differentiation from human pluripotent stem cells enables gene editing to model disease in kidney tubular epithelial cells. State-of-the-art human organoid cultures have potential as tools in basic and clinical research in renal, bladder, and prostatic diseases.