PD1hi cells associate with clusters of proliferating B-cells in marginal zone lymphoma

Background Abnormally sustained immune reactions drive B-cell proliferation in some cases of marginal zone lymphoma but the CD4.sup.+ T-cell subsets, which are likely to contribute to the B-cell responses in the tumour microenvironment, are not well characterised and neither has the spatial distribu...

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Published in:Diagnostic pathology 2018-09, Vol.13 (1), p.74-74, Article 74
Main Authors: Wickenden, Katherine, Nawaz, Nadia, Mamand, Sami, Kotecha, Deevia, Wilson, Amy L, Wagner, Simon D, Ahearne, Matthew J
Format: Article
Language:English
Subjects:
Breast cancer
CD4 antigen
Cell growth
Cell proliferation
Clustering
Correlation analysis
Diagnosis
Feasibility studies
Follicular helper T-cells
Foxp3 protein
Gene expression
Image processing
Immunohistochemistry
Infiltration
Investigations
Leukemia
Lymph nodes
Lymphocytes B
Lymphocytes T
Lymphoma
Lymphomas
Marginal zone lymphoma
Metastases
PD-1 protein
Spatial analysis
Spatial characteristics
Spatial distribution
Tumor microenvironment
Tumors
Workflow
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Summary:Background Abnormally sustained immune reactions drive B-cell proliferation in some cases of marginal zone lymphoma but the CD4.sup.+ T-cell subsets, which are likely to contribute to the B-cell responses in the tumour microenvironment, are not well characterised and neither has the spatial distribution of the different subsets in involved lymph nodes been investigated. Methods Employing a workflow of multiplex semi-automated immunohistochemistry combined with image processing we investigated association between infiltrating T-cells and proliferating lymphoma B-cells. Results Both total numbers of activating follicular helper (Tfh) cells (defined by high expression of PD1) and suppressive regulatory (Treg) T-cells (defined by FOXP3.sup.+ expression) and the Tfh:Treg ratio, assessed over relatively large areas of tissue, varied among cases of marginal zone lymphoma. We determined spatial distribution and demonstrated that PD1.sup.hi cells showed significantly more clustering than did FOXP3.sup.+. To investigate the association of infiltrating T-cells with lymphoma B-cells we employed Pearson correlation and Morisita-Horn index, statistical measures of interaction. We demonstrated that PD1.sup.hi cells were associated with proliferating B-cells and confirmed this by nearest neighbour analysis. Conclusions The unexpected architectural complexity of T-cell infiltration in marginal zone lymphoma, revealed in this study, further supports a key role for Tfh cells in driving proliferation of lymphoma B-cells. We demonstrate the feasibility of digital analysis of spatial architecture of T-cells within marginal zone lymphoma and future studies will be needed to determine the clinical importance of these observations. Keywords: Marginal zone lymphoma, Follicular helper T-cells, Spatial characteristics
ISSN:1746-1596
1746-1596
DOI:10.1186/s13000-018-0750-8