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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.
Theodros, Debebe; Murter, Benjamin M; Sidhom, John-William; Nirschl, Thomas R; Clark, David J; Chen, LiJun; Tam, Ada J; Blosser, Richard L; Schwen, Zeyad R; Johnson, Michael H; Pierorazio, Phillip M; Zhang, Hui; Ganguly, Sudipto; Pardoll, Drew M; Zarif, Jelani C.
Affiliation
  • Theodros D; Medical Scientist Training Program, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Graduate Program in Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Bloomberg-Kimmel Institute for Immunotherapy, Johns Hopkins University School of Medicine,
  • Murter BM; Bloomberg-Kimmel Institute for Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Sidhom JW; Medical Scientist Training Program, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Bloomberg-Kimmel Institute for Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Department of Biomedical Engineering, Johns Hopkins University School of Med
  • Nirschl TR; Bloomberg-Kimmel Institute for Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Pathobiology Graduate Program, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Department of Oncology, Johns Hopkins School of Medicine and The Sidney Kimmel Co
  • Clark DJ; Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Chen L; Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Tam AJ; Bloomberg-Kimmel Institute for Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Department of Oncology, Johns Hopkins School of Medicine and The Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA.
  • Blosser RL; Bloomberg-Kimmel Institute for Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Department of Oncology, Johns Hopkins School of Medicine and The Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA.
  • Schwen ZR; The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Johnson MH; The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Pierorazio PM; The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Zhang H; Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Ganguly S; Bloomberg-Kimmel Institute for Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Department of Oncology, Johns Hopkins School of Medicine and The Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA.
  • Pardoll DM; Graduate Program in Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Bloomberg-Kimmel Institute for Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Pathobiology Graduate Program, Johns Hopkins University School of Medicine, Balt
  • Zarif JC; Bloomberg-Kimmel Institute for Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Department of Oncology, Johns Hopkins School of Medicine and The Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA. Electronic address: jzarif1@jhmi.edu.
Mol Cell Proteomics ; 19(11): 1850-1859, 2020 11.
Article in En | MEDLINE | ID: mdl-32737216
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.
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Full text: 1 Database: MEDLINE Main subject: Leukocytes, Mononuclear / Carcinoma, Renal Cell / Biomarkers, Tumor / Leukocyte Common Antigens / Tumor Microenvironment / Immunotherapy / Kidney Neoplasms Type of study: Prognostic_studies Limits: Humans Language: En Year: 2020 Type: Article

Full text: 1 Database: MEDLINE Main subject: Leukocytes, Mononuclear / Carcinoma, Renal Cell / Biomarkers, Tumor / Leukocyte Common Antigens / Tumor Microenvironment / Immunotherapy / Kidney Neoplasms Type of study: Prognostic_studies Limits: Humans Language: En Year: 2020 Type: Article