title: Intratumoral CD14+ Cells and Circulating CD14+HLA-DRlo/neg Monocytes Correlate with Decreased Survival in Patients with Clear Cell Renal Cell Carcinoma.
abstract: OBJECTIVE
  Immunotherapeutic strategies to treat patients with renal cell carcinoma (RCC) offer new opportunities for disease management. Further improvements to immunotherapy will require additional understanding of the host response to RCC development.
  
  
  METHODS
  Using a novel approach to understanding the immune status of cancer patients, we previously showed that patients with a certain immune profile had decreased overall survival. Here, we examine in more detail the phenotypic changes in peripheral blood and the potential consequences of these changes in RCC patients.
  
  
  RESULTS
  We found that CD14(+)HLA-DR(lo/neg) monocytes were the most predominant phenotypic change in peripheral blood of RCC patients, elevated nearly 5-fold above the average levels measured in healthy volunteers. Intratumoral and peritumoral presence of CD14 cells was an independent prognostic factor for decreased survival in a cohort of 375 RCC patients. The amount of peripheral blood CD14(+)HLA-DR(lo/neg) monocytes was found to correlate with the intensity of CD14 staining in tumors, suggesting that the measurement of these cells in blood may be a suitable surrogate for monitoring patient prognosis. The interaction of monocytes and tumor cells triggers changes in both cell types with a loss of HLA-DR expression in monocytes, increases of monocyte survival factors such as GM-CSF in tumors, and increased production of angiogenic factors, including FGF2.
  
  
  CONCLUSIONS
  Our results suggest a model of mutually beneficial interactions between tumor cells and monocytes that adversely affect patient outcome.
authors.affiliation: Human Cellular Therapy Laboratory, Division of Transfusion Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Gustafson
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Division of Hematology, Sanford Health, Sioux Falls, South Dakota.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Bleeker
authors.affiliation: Division of Pediatric Hematology/Oncology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Deepti
authors.initials: D
authors.lastname: Warad
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Tollefson
authors.affiliation: Department of Urology, University of Florida, Gainesville, Florida.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Crispen
authors.affiliation: Human Cellular Therapy Laboratory, Division of Transfusion Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Peggy A
authors.initials: PA
authors.lastname: Bulur
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Harrington
authors.affiliation: Human Cellular Therapy Laboratory, Division of Transfusion Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Rebecca R
authors.initials: RR
authors.lastname: Laborde
authors.affiliation: Human Cellular Therapy Laboratory, Division of Transfusion Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota. Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Gastineau
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Bradley C
authors.initials: BC
authors.lastname: Leibovich
authors.affiliation: Department of Pathology, Mayo Clinic, Rochester, Minnesota.
authors.forename: John C
authors.initials: JC
authors.lastname: Cheville
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Eugene D
authors.initials: ED
authors.lastname: Kwon
authors.affiliation: Human Cellular Therapy Laboratory, Division of Transfusion Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota. dietz.allan@mayo.edu.
authors.forename: Allan B
authors.initials: AB
authors.lastname: Dietz
mesh_terms: D002292:Carcinoma, Renal Cell / Q000097:blood / Q000378:metabolism* / Q000401:mortality; D018920:Coculture Techniques; D015331:Cohort Studies; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006680:HLA Antigens / Q000378:metabolism*; D006684:HLA-DR Antigens / Q000378:metabolism; D064368:Healthy Volunteers; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007167:Immunotherapy / Q000379:methods; D007680:Kidney Neoplasms / Q000097:blood / Q000378:metabolism* / Q000401:mortality; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008297:Male; D009000:Monocytes / Q000166:cytology; D022423:Myeloid Cells / Q000276:immunology; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D010641:Phenotype; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D006680:HLA Antigens; D006684:HLA-DR Antigens; D018950:Lipopolysaccharide Receptors; D016222:Fibroblast Growth Factor 2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor