HIV infection is associated with compromised tumor microenvironment adaptive immune reactivity in Hodgkin lymphoma.
Details
Serval ID
serval:BIB_D343689440C2
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
HIV infection is associated with compromised tumor microenvironment adaptive immune reactivity in Hodgkin lymphoma.
Journal
Blood advances
ISSN
2473-9537 (Electronic)
ISSN-L
2473-9529
Publication state
Published
Issued date
24/12/2024
Peer-reviewed
Oui
Volume
8
Number
24
Pages
6215-6231
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Abstract
The impact of HIV infection on the tumor microenvironment (TME) of classic Hodgkin lymphoma (cHL), one of the most common comorbidities after HIV infection, is not well understood. Here, we have used multiplexed immunofluorescence and spatial transcriptomic analysis to dissect the impact of viral infections (Epstein-Barr virus [EBV] and HIV/EBV) on cHL TME. HIV-EBV+ cHL TME was characterized by higher cell densities of CD8high T cells coexpressing inhibitory receptors (PD-1 and TIGIT), macrophage subsets, and an in situ inflammatory molecular profile associated with increased expression of T-cell receptor (TCR) and B-cell receptor cell signaling pathways than HIV-EBV- cHL TME. Compared with HIV-EBV+, HIV+EBV+ cHL TME was characterized by significantly less CD8high T cells coexpressing PD-1 and TIGIT, a profile concomitant with significantly increased cell densities of CD155high neoplastic cells. Significant downregulation of in situ TCR signaling and upregulation of extracellular matrix reorganization pathways were found in HIV+EBV+ cHL TME, in line with an altered topological organization of CXCL13 and heparan sulfate, an extracellular matrix glycosaminoglycan. Our data reveal the complexity of the cellular and molecular composition of cHL TME in the presence of viral infections, with possible implications for combinatorial immunotherapies. Furthermore, the data suggest specific molecular targets and pathways for further investigation that could improve our understanding of possible mechanistic links between HIV and lymphomagenesis.
Keywords
Humans, Tumor Microenvironment/immunology, Hodgkin Disease/immunology, Hodgkin Disease/virology, HIV Infections/immunology, HIV Infections/complications, Adaptive Immunity, CD8-Positive T-Lymphocytes/immunology, CD8-Positive T-Lymphocytes/metabolism, Male, Epstein-Barr Virus Infections/complications, Epstein-Barr Virus Infections/immunology
Pubmed
Web of science
Open Access
Yes
Create date
09/08/2024 14:32
Last modification date
21/01/2025 7:12