Abstract
The role of the microenvironment in high-grade lymphoma is not well defined. In this report, we employ immunohistochemistry to characterise programmed death-1 (PD-1/CD279) and FoxP3 expression in 70 cases of diffuse large B-cell lymphoma (DLBCL). PD-1 is a surface marker characteristic of follicular helper T-cells whilst FoxP3 is characteristic of Tregs. We demonstrate variable infiltration with CD4+ T-cells (<10 to >50 % of all lymph node cells) and PD-1hi cells (0.1 to 1.5 % of all cells). CD4+ T-cells can be distributed in clusters or more diffusely and PD-1hi cells, but not FoxP3+ cells, are found in rosettes around lymphoma cells. Cases with high CD4+ T-cell numbers tended to have higher numbers of both PD-1hi and FoxP3+ cells. Cases with total CD4+ T-cell, PD-1hi and FoxP3+ numbers above the median associate with better clinical outcome. Overall, we demonstrate that infiltration by CD4+ T-cells, including both FoxP3+ and PD-1hi subsets, correlates with prognosis in DLBCL. In distinction to previous reported series, patients (91 %) were treated with rituximab-containing regimens, suggesting that the effects of CD4+ T-cell infiltration are maintained in the rituximab era. This work suggests that determinants of total CD4+ T-cell infiltration, either molecular characteristics of the lymphoma or the patients’ immune system, and not individual T-cell subsets, correlate with clinical outcome.
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Acknowledgments
Work in SDW’s laboratory is supported by the Kay Kendall Leukaemia Fund and the Leicester Haematology Research Fund. MJA was supported by an unrestricted grant from Roche. We also wish to thank the Database Manager, Judy Maynard-Mills, for her assistance with this project. Part of this work was presented as a poster at the American Society of Hematology, San Diego, CA, USA, 2011.
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Ahearne, M.J., Bhuller, K., Hew, R. et al. Expression of PD-1 (CD279) and FoxP3 in diffuse large B-cell lymphoma. Virchows Arch 465, 351–358 (2014). https://doi.org/10.1007/s00428-014-1615-5
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DOI: https://doi.org/10.1007/s00428-014-1615-5