title: Mass Cytometry of Follicular Lymphoma Tumors Reveals Intrinsic Heterogeneity in Proteins Including HLA-DR and a Deficit in Nonmalignant Plasmablast and Germinal Center B-Cell Populations.
abstract: Follicular lymphoma (FL) is an indolent non-Hodgkin lymphoma that has a risk of transformation to more aggressive lymphoma. Relatively little is known about the nonmalignant B-cell and T-cell subset composition within the tumor microenvironment and whether altered phenotypes are associated with patterns of lymphoma B-cell heterogeneity.
  
  
  
  Two mass cytometry (CyTOF) panels were designed to immunophenotype B and T cells in FL tumors. Populations of malignant B cells, nonmalignant B cells, and T cells from each FL tumor were identified and their phenotypes compared to B and T cells from healthy human tonsillar tissue.
  
  
  
  Diversity in cellular phenotype between tumors was greater for the malignant B cells than for nonmalignant B or T cells. The malignant B-cell population bore little phenotypic similarity to any healthy B-cell subset, and unexpectedly clustered closer to naïve B-cell populations than GC B-cell populations. Among the nonmalignant B cells within FL tumors, a significant lack of GC and plasmablast B cells was observed relative to tonsil controls. In contrast, nonmalignant T cells in FL tumors were present at levels similar to their cognate tonsillar T-cell subsets.
  
  
  
  Mass cytometry revealed that diverse HLA-DR expression on FL cells within individual tumors contributed greatly to tumor heterogeneity. Both malignant and nonmalignant B cells in the tumor bore little phenotypic resemblance to healthy GC B cells despite the presence of T follicular helper cells in the tumor. These findings suggest that ongoing signaling interactions between malignant B cells and intra-tumor T cells shape the tumor microenvironment. © 2016 International Clinical Cytometry Society.
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Cara Ellen
authors.initials: CE
authors.lastname: Wogsland
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Allison Rae
authors.initials: AR
authors.lastname: Greenplate
authors.affiliation: Department of Oncology, Oslo University Hospital, Oslo, Norway.
authors.forename: Arne
authors.initials: A
authors.lastname: Kolstad
authors.affiliation: Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.|Centre for Cancer Biomedicine, University of Oslo, Oslo, Norway.
authors.forename: June Helen
authors.initials: JH
authors.lastname: Myklebust
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee.|Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee.
authors.forename: Jonathan Michael
authors.initials: JM
authors.lastname: Irish
authors.affiliation: Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.|Centre for Cancer Biomedicine, University of Oslo, Oslo, Norway.
authors.forename: Kanutte
authors.initials: K
authors.lastname: Huse
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology*; D005434:Flow Cytometry; D018858:Germinal Center / Q000276:immunology / Q000473:pathology*; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000473:pathology; D008224:Lymphoma, Follicular / Q000175:diagnosis / Q000276:immunology*; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D006684:HLA-DR Antigens
keywords: follicular lymphoma; human tissue; mass cytometry (CyTOF); tumor-infiltrating lymphocyte