Mass cytometry of follicular lymphoma tumors reveals intrinsic heterogeneity in proteins including HLA-DR and a deficit in non-malignant plasmablast and germinal center B cell populations
Wogsland, C.E., Greenplate, A.R., Kolstad, A. et al.
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 non-malignant 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, non-malignant 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 non-malignant 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 non-malignant B cells within FL tumors, a significant lack of GC and plasmablast B cells was observed relative to tonsil controls. In contrast, non-malignant 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 non-malignant 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.
Wogsland, C.E., Greenplate, A.R., Kolstad, A. et al. "Mass cytometry of follicular lymphoma tumors reveals intrinsic heterogeneity in proteins including HLA-DR and a deficit in non-malignant plasmablast and germinal center B cell populations" Cytometry Part B Clinical Cytometry (2016): 79–87