Lymphocyte predominant <scp>Hodgkin</scp> lymphoma, antigen‐driven after all?

Poppema, Sibrandes

doi:10.1002/path.5567

Cited by 5 publications

(2 citation statements)

References 94 publications

(110 reference statements)

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“…The depletion of CD4+FOXP3+ cells across all NLPHL cases (including Fan histological patterns A, C and E in this study) points to a TME signature necessary for lymphomagenesis. NLPHL development has been shown to be related to chronic stimulation by driver antigens in a Tfh-dependent manner ( 28 ). This may include exogenous microbial antigens as exemplified by Thurner et al.…”

Section: Discussionmentioning

confidence: 99%

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

Panayi,

Akarca,

Ramsay

et al. 2023

Front. Oncol.

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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.

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Section: Discussionmentioning

confidence: 99%

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

Panayi,

Akarca,

Ramsay

et al. 2023

Front. Oncol.

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“…Moraxella catarrhalis is associated with several common childhood infectious illnesses and could be an antigenic driver. 10 …”

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confidence: 99%

Progress in understanding the biology of nodular lymphocyte-predominant Hodgkin lymphoma

Straus

2021

haematol

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Intra‐tumoral and peripheral blood TIGIT and PD‐1 as immune biomarkers in nodular lymphocyte predominant Hodgkin lymphoma

Gunawardana,

Law,

Sabdia

et al. 2024

American J Hematol

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In classical Hodgkin lymphoma (cHL), responsiveness to immune‐checkpoint blockade (ICB) is associated with specific tumor microenvironment (TME) and peripheral blood features. The role of ICB in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is not established. To gain insights into its potential in NLPHL, we compared TME and peripheral blood signatures between HLs using an integrative multiomic analysis. A discovery/validation approach in 121 NLPHL and 114 cHL patients highlighted >2‐fold enrichment in programmed cell death‐1 (PD‐1) and T‐cell Ig and ITIM domain (TIGIT) gene expression for NLPHL versus cHL. Multiplex imaging showed marked increase in intra‐tumoral protein expression of PD‐1+ (and/or TIGIT+) CD4+ T‐cells and PD‐1+CD8+ T‐cells in NLPHL compared to cHL. This included T‐cells that rosetted with lymphocyte predominant (LP) and Hodgkin Reed–Sternberg (HRS) cells. In NLPHL, intra‐tumoral PD‐1+CD4+ T‐cells frequently expressed TCF‐1, a marker of heightened T‐cell response to ICB. The peripheral blood signatures between HLs were also distinct, with higher levels of PD‐1+TIGIT+ in TH1, TH2, and regulatory CD4+ T‐cells in NLPHL versus cHL. Circulating PD‐1+CD4+ had high levels of TCF‐1. Notably, in both lymphomas, highly expanded populations of clonal TIGIT+PD‐1+CD4+ and TIGIT+PD‐1+CD8+ T‐cells in the blood were also present in the TME, indicating that immune‐checkpoint expressing T‐cells circulated between intra‐tumoral and blood compartments. In in vitro assays, ICB was capable of reducing rosette formation around LP and HRS cells, suggesting that disruption of rosetting may be a mechanism of action of ICB in HL. Overall, results indicate that further evaluation of ICB is warranted in NLPHL.

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Lymphocyte predominant Hodgkin lymphoma, antigen‐driven after all?

Cited by 5 publications

References 94 publications

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

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

Progress in understanding the biology of nodular lymphocyte-predominant Hodgkin lymphoma

Intra‐tumoral and peripheral blood TIGIT and PD‐1 as immune biomarkers in nodular lymphocyte predominant Hodgkin lymphoma

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