Hodgkin/Reed-Sternberg cells induce GPNMB expression and release from macrophages to suppress T-cell responses to the Epstein-Barr virus-encoded LMP2A protein

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F25%3A73632840" target="_blank" >RIV/61989592:15110/25:73632840 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00098892:_____/25:10158917

Výsledek na webu

<a href="https://haematologica.org/article/view/haematol.2024.285319" target="_blank" >https://haematologica.org/article/view/haematol.2024.285319</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3324/haematol.2024.285319" target="_blank" >10.3324/haematol.2024.285319</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Hodgkin/Reed-Sternberg cells induce GPNMB expression and release from macrophages to suppress T-cell responses to the Epstein-Barr virus-encoded LMP2A protein

Popis výsledku v původním jazyce

Classical Hodgkin lymphoma (cHL) is characterized by the presence of Hodgkin-Reed-Sternberg (HRS) cells surrounded by a prominent inflammatory tumor microenvironment (TME). Although the TME is thought to prevent immune recognition of HRS cells by tumor-specific T cells, the mechanisms responsible are poorly understood. Here, we show that tumor-associated macrophages (TAM) in the TME of cHL strongly express glycoprotein non-metastatic B (GPNMB). Co-culture with cHL cell lines induced the M2 polarization of macrophages, which was accompanied by increased surface expression of GPNMB and its release as a soluble form. Importantly, soluble recombinant GPNMB (rGPNMB) inhibited CD8+ T-cell recognition of Epstein-Barr virus (EBV)-derived tumor epitopes in cHL cells, suggesting that inhibiting GPNMB in the cHL TME could enhance anti-tumor immune responses. cHL is characterized by single malignant HRS cells surrounded by a pro-inflammatory tumor microenvironment (TME) that supports HRS cell survival, growth and immune escape. The EBV genome is present in HRS cells in 30-50% of cHL and expresses the immunologically subdominant EBV latent proteins, Epstein-Barr nuclear antigen 1 and latent membrane proteins, LMP1 and LMP2A.1 Cells expressing LMP1 and LMP2A are sensitive to lysis by EBV-specific cytotoxic CD8+ T cells in vitro. Moreover, EBV-specific CD8+ T cells have been shown to be present in the cHL TME. These data suggest that immune suppressive mechanisms operate in the TME of EBV+ cHL.

Název v anglickém jazyce

Hodgkin/Reed-Sternberg cells induce GPNMB expression and release from macrophages to suppress T-cell responses to the Epstein-Barr virus-encoded LMP2A protein

Popis výsledku anglicky

Classical Hodgkin lymphoma (cHL) is characterized by the presence of Hodgkin-Reed-Sternberg (HRS) cells surrounded by a prominent inflammatory tumor microenvironment (TME). Although the TME is thought to prevent immune recognition of HRS cells by tumor-specific T cells, the mechanisms responsible are poorly understood. Here, we show that tumor-associated macrophages (TAM) in the TME of cHL strongly express glycoprotein non-metastatic B (GPNMB). Co-culture with cHL cell lines induced the M2 polarization of macrophages, which was accompanied by increased surface expression of GPNMB and its release as a soluble form. Importantly, soluble recombinant GPNMB (rGPNMB) inhibited CD8+ T-cell recognition of Epstein-Barr virus (EBV)-derived tumor epitopes in cHL cells, suggesting that inhibiting GPNMB in the cHL TME could enhance anti-tumor immune responses. cHL is characterized by single malignant HRS cells surrounded by a pro-inflammatory tumor microenvironment (TME) that supports HRS cell survival, growth and immune escape. The EBV genome is present in HRS cells in 30-50% of cHL and expresses the immunologically subdominant EBV latent proteins, Epstein-Barr nuclear antigen 1 and latent membrane proteins, LMP1 and LMP2A.1 Cells expressing LMP1 and LMP2A are sensitive to lysis by EBV-specific cytotoxic CD8+ T cells in vitro. Moreover, EBV-specific CD8+ T cells have been shown to be present in the cHL TME. These data suggest that immune suppressive mechanisms operate in the TME of EBV+ cHL.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30205 - Hematology

Projekt

<a href="/cs/project/EF16_019%2F0000868" target="_blank" >EF16_019/0000868: Molekulární, buněčný a klinický přístup ke zdravému stárnutí</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

HAEMATOLOGICA

ISSN

0390-6078

e-ISSN

1592-8721

Svazek periodika

110

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

IT - Italská republika

Počet stran výsledku

7

Strana od-do

193-199

Kód UT WoS článku

001391817200021

EID výsledku v databázi Scopus

2-s2.0-85214300569