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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
Author(s) -
Wogsland Cara Ellen,
Greenplate Allison Rae,
Kolstad Arne,
Myklebust June Helen,
Irish Jonathan Michael,
Huse Kanutte
Publication year - 2017
Publication title -
cytometry part b: clinical cytometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.646
H-Index - 61
eISSN - 1552-4957
pISSN - 1552-4949
DOI - 10.1002/cyto.b.21498
Subject(s) - germinal center , biology , mass cytometry , immunophenotyping , b cell , follicular lymphoma , population , lymphoma , phenotype , pathology , immunology , cancer research , flow cytometry , medicine , antibody , genetics , environmental health , gene
Background 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. Methods 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. Results 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. Conclusion 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