Panayi, C;
Akarca, AU;
Ramsay, AD;
Shankar, AG;
Falini, B;
Piris, MA;
Linch, D;
(2023)
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
, 13
, Article 1267604. 10.3389/fonc.2023.1267604.
Preview |
Text
Akarca_Microenvironmental immune cell alterations across the spectrum of nodular lymphocyte predominant Hodgkin lymphoma and T-cell_VoR.pdf - Published Version Download (18MB) | Preview |
Abstract
BACKGROUND: The 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. METHODS: We 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. RESULTS: FOXP3-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. DISCUSSION: These 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.
| Type: | Article |
|---|---|
| Title: | Microenvironmental immune cell alterations across the spectrum of nodular lymphocyte predominant Hodgkin lymphoma and T-cell/histiocyte-rich large B-cell lymphoma |
| Location: | Switzerland |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fonc.2023.1267604 |
| Publisher version: | https://doi.org/10.3389/fonc.2023.1267604 |
| Language: | English |
| Additional information: | © 2023 Panayi, Akarca, Ramsay, Shankar, Falini, Piris, Linch and Marafioti. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| Keywords: | Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), T-cell/histiocyte-rich large B-cell lymphoma, tumor microenvironment, immune checkpoints, lymphoma biology, multispectral immunofluorescence |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Pathology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10180961 |
Archive Staff Only
 |
View Item |
