Motzer RJ, Tannir NM, McDermott DF, Arén Frontera O, Melichar B, Choueiri TK, Plimack ER, Barthélémy P, Porta C, George S, et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018;378:1277–90.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rini BI, Plimack ER, Stus V, Gafanov R, Hawkins R, Nosov D, Pouliot F, Alekseev B, Soulières D, Melichar B, et al. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019;380:1116–27.

Article  CAS  PubMed  Google Scholar 

Albiges L, Tannir NM, Burotto M, McDermott D, Plimack ER, Barthélémy P, Porta C, Powles T, Donskov F, George S, et al. Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended 4-year follow-up of the phase III CheckMate 214 trial. ESMO Open. 2020;5: e001079.

Article  PubMed  PubMed Central  Google Scholar 

Tannir NM, Signoretti S, Choueiri TK, McDermott DF, Motzer RJ, Flaifel A, Pignon JC, Ficial M, Frontera OA, George S, et al. Efficacy and safety of nivolumab plus ipilimumab versus sunitinib in first-line treatment of patients with advanced sarcomatoid renal cell carcinoma. Clin Cancer Res. 2021;27:78–86.

Article  CAS  PubMed  Google Scholar 

Miao D, Margolis CA, Gao W, Voss MH, Li W, Martini DJ, Norton C, Bossé D, Wankowicz SM, Cullen D, et al. Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma. Science. 2018;359:801–6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chakiryan NH, Kim Y, Berglund A, Chang A, Kimmel GJ, Hajiran A, Nguyen J, Moran-Segura C, Saeed-Vafa D, Katende EN, et al. Geospatial characterization of immune cell distributions and dynamics across the microenvironment in clear cell renal cell carcinoma. J Immunother Cancer. 2023;11: e006195.

Article  PubMed  PubMed Central  Google Scholar 

Hakimi AA, Voss MH, Kuo F, Sanchez A, Liu M, Nixon BG, Vuong L, Ostrovnaya I, Chen Y-B, Reuter V, et al. Transcriptomic profiling of the tumor microenvironment reveals distinct subgroups of clear cell renal cell cancer: data from a randomized phase III trial. Cancer Discov. 2019;9:510–25.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chevrier S, Levine JH, Zanotelli VRT, Silina K, Schulz D, Bacac M, Ries CH, Ailles L, Jewett MAS, Moch H, et al. An immune atlas of clear cell renal cell carcinoma. Cell. 2017;169:736-749.e718.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Şenbabaoğlu Y, Gejman RS, Winer AG, Liu M, Van Allen EM, de Velasco G, Miao D, Ostrovnaya I, Drill E, Luna A, et al. Tumor immune microenvironment characterization in clear cell renal cell carcinoma identifies prognostic and immunotherapeutically relevant messenger RNA signatures. Genome Biol. 2016;17:231.

Article  PubMed  PubMed Central  Google Scholar 

Young MD, Mitchell TJ, Vieira Braga FA, Tran MGB, Stewart BJ, Ferdinand JR, Collord G, Botting RA, Popescu DM, Loudon KW, et al. Single-cell transcriptomes from human kidneys reveal the cellular identity of renal tumors. Science. 2018;361:594–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Krishna C, DiNatale RG, Kuo F, Srivastava RM, Vuong L, Chowell D, Gupta S, Vanderbilt C, Purohit TA, Liu M, et al. Single-cell sequencing links multiregional immune landscapes and tissue-resident T cells in ccRCC to tumor topology and therapy efficacy. Cancer Cell. 2021;39:662-677.e666.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang Y, Narayanan SP, Mannan R, Raskind G, Wang X, Vats P, Su F, Hosseini N, Cao X, Kumar-Sinha C, et al. Single-cell analyses of renal cell cancers reveal insights into tumor microenvironment, cell of origin, and therapy response. Proc Natl Acad Sci U S A. 2021;118:e2103240118.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liu J, Tran V, Vemuri VNP, Byrne A, Borja M, Kim YJ, Agarwal S, Wang R, Awayan K, Murti A, et al. Concordance of MERFISH spatial transcriptomics with bulk and single-cell RNA sequencing. Life Sci Alliance. 2023;6. https://doi.org/10.26508/lsa.202201701.

He S, Bhatt R, Brown C, Brown EA, Buhr DL, Chantranuvatana K, Danaher P, Dunaway D, Garrison RG, Geiss G, et al. High-plex imaging of RNA and proteins at subcellular resolution in fixed tissue by spatial molecular imaging. Nat Biotechnol. 2022;40:1794–806.

Article  CAS  PubMed  Google Scholar 

Chahoud J, Anderson ARA, Zhang J, Brown J, Gatenby RA. Evolutionary dynamics and intermittent therapy for metastatic cancers. J Clin Oncol. 2023;41:4469–71.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gatenby RA, Brown JS. The evolution and ecology of resistance in cancer therapy. Cold Spring Harb Perspect Med. 2020;10. https://doi.org/10.1101/cshperspect.a040972.

Li R, Ferdinand JR, Loudon KW, Bowyer GS, Laidlaw S, Muyas F, Mamanova L, Neves JB, Bolt L, Fasouli ES, et al. Mapping single-cell transcriptomes in the intra-tumoral and associated territories of kidney cancer. Cancer Cell. 2022;40:1583-1599.e1510.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Creed JH, Wilson CM, Soupir AC, Colin-Leitzinger CM, Kimmel GJ, Ospina OE, Chakiryan NH, Markowitz J, Peres LC, Coghill A, Fridley BL. spatialTIME and iTIME: R package and Shiny application for visualization and analysis of immunofluorescence data. Bioinformatics. 2021;37:4584–6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lähnemann D, Köster J, Szczurek E, McCarthy DJ, Hicks SC, Robinson MD, Vallejos CA, Campbell KR, Beerenwinkel N, Mahfouz A, et al. Eleven grand challenges in single-cell data science. Genome Biol. 2020;21:31.

Article  PubMed  PubMed Central  Google Scholar 

Jerby-Arnon L, Shah P, Cuoco MS, Rodman C, Su MJ, Melms JC, Leeson R, Kanodia A, Mei S, Lin JR, et al. A cancer cell program promotes T cell exclusion and resistance to checkpoint blockade. Cell. 2018;175:984-997.e924.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Clark DJ, Dhanasekaran SM, Petralia F, Pan J, Song X, Hu Y, da Veiga LF, Reva B, Lih TM, Chang HY, et al. Integrated proteogenomic characterization of clear cell renal cell carcinoma. Cell. 2019;179:964-983.e931.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lonsdale J, Thomas J, Salvatore M, Phillips R, Lo E, Shad S, Hasz R, Walters G, Garcia F, Young N, et al. The Genotype-Tissue Expression (GTEx) project. Nat Genet. 2013;45:580–5.

Article  CAS  Google Scholar 

Nallandhighal S, Vince R, Karim R, Groves S, Stangl-Kremser J, Russell C, Hu K, Pham T, Cani AK, Liu CJ, et al. Molecular characterization of clear cell renal cell carcinoma reveals prognostic significance of epithelial-mesenchymal transition gene expression signature. Eur Urol Oncol. 2022;5:92–9.

Article  PubMed  Google Scholar 

Zhang Y, Narayanan SP, Mannan R, Raskind G, Wang X, Vats P, Su F, Hosseini N, Cao X, Kumar-Sinha C, et al. Single-cell analyses of renal cell cancers reveal insights into tumor microenvironment, cell of origin, and therapy response. Proc Natl Acad Sci U SA. 2021;118:e2103240118.

Article  CAS  Google Scholar 

Liu F, Wang P, Sun W, Jiang Y, Gong Q. Identification of ligand-receptor pairs associated with tumour characteristics in clear cell renal cell carcinoma. Front Immunol. 2022;13:874056.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wu Y, Terekhanova NV, Caravan W, Naser Al Deen N, Lal P, Chen S, Mo CK, Cao S, Li Y, Karpova A, et al. Epigenetic and transcriptomic characterization reveals progression markers and essential pathways in clear cell renal cell carcinoma. Nat Commun. 2023;14:1681.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kalluri R. The biology and function of fibroblasts in cancer. Nat Rev Cancer. 2016;16:582–98.

Article  CAS  PubMed  Google Scholar 

Rybarczyk A, Klacz J, Wronska A, Matuszewski M, Kmiec Z, Wierzbicki PM. Overexpression of the YAP1 oncogene in clear cell renal cell carcinoma is associated with poor outcome. Oncol Rep. 2017;38:427–39.

Article  CAS  PubMed  Google Scholar 

Poma AM, Torregrossa L, Bruno R, Basolo F, Fontanini G. Hippo pathway affects survival of cancer patients: extensive analysis of