Microenvironmental immune cell alterations across the spectrum of nodular lymphocyte predominant Hodgkin lymphoma and T-cell/histiocyte-rich large B-cell lymphoma

Frontiers in Oncology

Oncology

Ananth G. Shankar¹  Christos Panayi²  Alan D. Ramsay²  Teresa Marafioti³  Brunangelo Falini⁴  Miguel A. Piris⁵  David Linch⁶  Ayse U. Akarca⁷ 

[1] Children and Young People’s Cancer Services, University College London Hospitals NHS Foundation Trust, London, United Kingdom;Department of Cellular Pathology, University College London Hospitals NHS Foundation Trust, London, United Kingdom;Department of Cellular Pathology, University College London Hospitals NHS Foundation Trust, London, United Kingdom;University College London (UCL) Cancer Institute, University College London, London, United Kingdom;Institute of Hematology and Center for Haemato-Oncological Research (CREO), University of Perugia and Santa Maria della Misericordia Hospital, Perugia, Italy;Pathology Department, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Madrid, Spain;Research Department of Haematology, Cancer Institute, University College London, London, United Kingdom;University College London (UCL) Cancer Institute, University College London, London, United Kingdom;

关键词: nodular lymphocyte predominant Hodgkin lymphoma (NLPHL);    T-cell/histiocyte-rich large B-cell lymphoma;    tumor microenvironment;    immune checkpoints;    lymphoma biology;    multispectral immunofluorescence;   

DOI  :  10.3389/fonc.2023.1267604

 received in 2023-07-26, accepted in 2023-09-18,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundThe clinicopathological spectrum of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), also known as nodular lymphocyte predominant B-cell lymphoma, partially overlaps with T-cell/histiocyte-rich large B-cell lymphoma (THRLCBL). NLPHL histology may vary in architecture and B-cell/T-cell composition of the tumour microenvironment. However, the immune cell phenotypes accompanying different histological patterns remain poorly characterised.MethodsWe applied a multiplexed immunofluorescence workflow to identify differential expansion/depletion of multiple microenvironmental immune cell phenotypes between cases of NLPHL showing different histological patterns (as described by Fan et al, 2003) and cases of THRLBCL.ResultsFOXP3-expressing T-regulatory cells were conspicuously depleted across all NLPHL cases. As histology progressed to variant Fan patterns C and E of NLPHL and to THRLBCL, there were progressive expansions of cytotoxic granzyme-B-expressing natural killer and CD8-positive T-cells, PD1-expressing CD8-positive T-cells, and CD163-positive macrophages including a PDL1-expressing subset. These occurred in parallel to depletion of NKG2A-expressing natural killer and CD8-positive T-cells.DiscussionThese findings provide new insights on the immunoregulatory mechanisms involved in NLPHL and THLRBCL pathogenesis, and are supportive of an increasingly proposed biological continuum between these two lymphomas. Additionally, the findings may help establish new biomarkers of high-risk disease, which could support a novel therapeutic program of immune checkpoint interruption targeting the PD1:PDL1 and/or NKG2A:HLA-E axes in the management of high-risk NLPHL and THRLBCL.

【 授权许可】

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Copyright © 2023 Panayi, Akarca, Ramsay, Shankar, Falini, Piris, Linch and Marafioti