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Epitranscriptomics & Cancer Adaptation : A.David

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Our research work focuses on the contribution of post-transcriptional mechanisms on cancer cell adaptation, in particular RNA epigenetic & translational control.

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Group name EquipeELC
Item Type Journal Article
Title Characterisation of tumour microenvironment and immune checkpoints in primary central nervous system diffuse large B cell lymphomas
Creator Alame et al.
Author Marion Pirel
Author Valérie Costes-Martineau
Author Luc Bauchet
Author Michel Fabbro
Author Alicia Tourneret
Author Laura De Oliveira
Author Luc Durand
Author Pascal Roger
Author Samia Gonzalez
Author Valère Cacheux
Author Valérie Rigau
Author Vanessa Szablewski
Abstract Primary central nervous system diffuse large B cell lymphoma (PCNS-DLBCL) is a rare and aggressive entity of diffuse large B cell lymphoma (DLBCL). Elements of the tumour microenvironment (TME) including tumour-infiltrating lymphocytes (TILs) and tumour-associated macrophages (TAMs) have been associated with survival in DLBCL but their composition and prognostic impact in PCNS-DLBCL are unknown. Programmed cell death-1 (PD1)/programmed death-ligand 1 (PD-L1) immune checkpoint may represent a therapeutic option. Here, we aimed to characterise PD1/PDL1 immune checkpoints and the composition of the TME in PCNS-DLBCL. We collected tumour tissue and clinical data from 57 PCNS-DLBCL and used immunohistochemistry to examine TAMs (CD68, CD163), TILs (CD3, CD4, CD8, PD1) and tumour B cells (PAX5/PDL1 double stains, PDL1). The PDL1 gene was evaluated by fluorescence in situ hybridization (FISH). PAX5/PDL1 identified PDL1 expression by tumour B cells in 10/57 cases (17.5%). PDL1 gene translocation was a recurrent cytogenetic alteration in PNCS-DLBCL (8/47.17%) and was correlated with PDL1 positive expression in tumour B cells. The TME consisted predominantly of CD163 (+) M2 TAMs and CD8 (+) TILs. Most TAMs expressed PDL1 and most TILs expressed PD1. The density of TAMs and TILs did not associate with outcome. We showed that expression of PD1 on TILs and PDL1 on TAMs, but not the expression of PDL1 on tumour B cells was correlated with better prognosis. These findings support a significant role of TME composition and PD1/PDL1 crosstalk in PCNS-DLBCL pathogenesis and bring new insights to the targeted therapy of this aggressive lymphoma.
Publication Virchows Archiv: An International Journal of Pathology
Volume 476
Issue 6
Pages 891-902
Date 2020-06
Journal Abbr Virchows Arch
Language eng
DOI 10.1007/s00428-019-02695-6
ISSN 1432-2307
Library Catalog PubMed
Extra PMID: 31811434
Tags Adult, Aged, Aged, 80 and over, B7-H1 Antigen, Biomarkers, Tumor, Central Nervous System Neoplasms, clinic, Female, France, Humans, Immune checkpoints, In Situ Hybridization, Fluorescence, Lymphocytes, Tumor-Infiltrating, Lymphoma, Large B-Cell, Diffuse, Macrophages, Male, Middle Aged, PDL1, Primary central nervous system diffuse large B cell lymphoma, Prognosis, Programmed Cell Death 1 Receptor, Retrospective Studies, Tumor Microenvironment, Tumour microenvironment
Date Added 2021/03/19 - 17:04:11
Date Modified 2021/03/19 - 17:10:33
Notes and Attachments PubMed entry (Attachment)


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