{"doi":"10.1074/mcp.ra120.002049","title":"High-dimensional Cytometry (ExCYT) and Mass Spectrometry of Myeloid Infiltrate in Clinically Localized Clear Cell Renal Cell Carcinoma Identifies Novel Potential Myeloid Targets for Immunotherapy","abstract":"Renal Cell Carcinoma (RCC) is one of the most commonly diagnosed cancers worldwide with research efforts dramatically improving understanding of the biology of the disease. To investigate the role of the immune system in treatment-naïve clear cell Renal Cell Carcinoma (ccRCC), we interrogated the immune infiltrate in patient-matched ccRCC tumor samples, benign normal adjacent tissue (NAT) and peripheral blood mononuclear cells (PBMCs isolated from whole blood, focusing our attention on the myeloid cell infiltrate. Using flow cytometric, MS, and ExCYT analysis, we discovered unique myeloid populations in PBMCs across patient samples. Furthermore, normal adjacent tissues and ccRCC tissues contained numerous myeloid populations with a unique signature for both tissues. Enrichment of the immune cell (CD45+) fraction and subsequent gene expression analysis revealed a number of myeloid-related genes that were differentially expressed. These data provide evidence, for the first time, of an immunosuppressive and pro-tumorigenic role of myeloid cells in early, clinically localized ccRCC. The identification of a number of immune proteins for therapeutic targeting provides a rationale for investigation into the potential efficacy of earlier intervention with single-agent or combination immunotherapy for ccRCC. Renal Cell Carcinoma (RCC) is one of the most commonly diagnosed cancers worldwide with research efforts dramatically improving understanding of the biology of the disease. To investigate the role of the immune system in treatment-naïve clear cell Renal Cell Carcinoma (ccRCC), we interrogated the immune infiltrate in patient-matched ccRCC tumor samples, benign normal adjacent tissue (NAT) and peripheral blood mononuclear cells (PBMCs isolated from whole blood, focusing our attention on the myeloid cell infiltrate. Using flow cytometric, MS, and ExCYT analysis, we discovered unique myeloid populations in PBMCs across patient samples. Furthermore, normal adjacent tissues and ccRCC tissues contained numerous myeloid populations with a unique signature for both tissues. Enrichment of the immune cell (CD45+) fraction and subsequent gene expression analysis revealed a number of myeloid-related genes that were differentially expressed. These data provide evidence, for the first time, of an immunosuppressive and pro-tumorigenic role of myeloid cells in early, clinically localized ccRCC. The identification of a number of immune proteins for therapeutic targeting provides a rationale for investigation into the potential efficacy of earlier intervention with single-agent or combination immunotherapy for ccRCC. Renal cell carcinoma (RCC) is one of the most commonly diagnosed cancers with numerous molecular and histological features identified leading to tailored therapeutic approaches (1Capitanio U. et al.Epidemiology of renal cell carcinoma.Eur Urol. 2019; 75: 74-84Abstract Full Text Full Text PDF PubMed Scopus (491) Google Scholar, 2Hsieh J.J. Purdue M.P. Signoretti S. Swanton C. Albiges L. Schmidinger M. Heng D.Y. Larkin J. Ficarra V. Renal cell carcinoma.Nat. Rev. Dis. Primers. 2017; 3: 17009Crossref PubMed Scopus (1007) Google Scholar). Standard of care options for clinically localized RCC include partial and radical nephrectomy, active surveillance, and thermal ablation (3Campbell S. Uzzo R.G. Allaf M.E. Bass E.B. Cadeddu J.A. Chang A. Clark P.E. Davis B.J. Derweesh I.H. Giambarresi L. Gervais D.A. Hu S.L. Lane B.R. Leibovich B.C. Pierorazio P.M. Renal mass and localized renal cancer: AUA Guideline.J. Urol. 2017; 198: 520-529Crossref PubMed Scopus (736) Google Scholar). However, up to 30% of patients progress and develop metastatic disease that is associated with a high mortality rate (4Meskawi M. Sun M. Trinh Q.-D. Bianchi M. Hansen J. Tian Z. Rink M. Ismail S. Shariat S.F. Montorsi F. Perrotte P. Karakiewicz P.I. A review of integrated staging systems for renal cell carcinoma.Eur. Urol. 2012; 62: 303-314Abstract Full Text Full Text PDF","journal":"Molecular & Cellular Proteomics","year":2020,"id":112456,"datarank":0.24214470980720826,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.034200555639224625,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.034200555639224625,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":2,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.956,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":500885,"name":"Benjamin Murter","orcid":"0000-0003-3035-3782","position":1,"is_corresponding":false},{"id":299296,"name":"John-William Sidhom","orcid":"0000-0002-5575-0285","position":2,"is_corresponding":false},{"id":263701,"name":"Thomas R. Nirschl","orcid":"0000-0002-3329-6229","position":3,"is_corresponding":false},{"id":108239,"name":"David Clark","orcid":"0000-0003-0527-8469","position":4,"is_corresponding":false},{"id":531962,"name":"Li‐Jun Chen","orcid":"0000-0002-3012-4018","position":5,"is_corresponding":false},{"id":228366,"name":"Ada Tam","orcid":"0000-0001-6828-5290","position":6,"is_corresponding":false},{"id":228367,"name":"Richard L. Blosser","orcid":"0000-0002-8606-769X","position":7,"is_corresponding":false},{"id":531963,"name":"Zeyad Schwen","orcid":"0000-0001-7334-3600","position":8,"is_corresponding":false},{"id":91910,"name":"Michael H. Johnson","orcid":"0000-0003-4393-2468","position":9,"is_corresponding":false},{"id":531964,"name":"Phillip M. Pierorazio","orcid":"0000-0003-0766-9981","position":10,"is_corresponding":false},{"id":51843,"name":"Hui Zhang","orcid":"0000-0001-8726-7098","position":11,"is_corresponding":false},{"id":328465,"name":"Sudipto Ganguly","orcid":"0000-0002-2662-8897","position":12,"is_corresponding":false},{"id":59439,"name":"Drew M. Pardoll","orcid":"0000-0001-6215-1013","position":13,"is_corresponding":false},{"id":228418,"name":"Jelani C. Zarif","orcid":"0000-0003-3880-2124","position":14,"is_corresponding":false},{"id":531961,"name":"Debebe Theodros","orcid":"0000-0002-2189-5013","position":0,"is_corresponding":true}],"reference_count":34,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:13:13.874980Z","pmid":"32737216","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}