1. Characterisation of tumour microenvironment and immune checkpoints in primary central nervous system diffuse large B cell lymphomas
- Author
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Laura De Oliveira, Valère Cacheux, Melissa Alame, Pascal Roger, Valérie Rigau, Valérie Costes-Martineau, Samia Gonzalez, Marion Pirel, Michel Fabbro, Alicia Tourneret, Luc Durand, Luc Bauchet, Vanessa Szablewski, Département d'hématologie biologique[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Biopathologie [CHRU Montpellier], Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Gui de Chauliac, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), and Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)
- Subjects
Male ,0301 basic medicine ,Programmed Cell Death 1 Receptor ,Aggressive lymphoma ,B7-H1 Antigen ,Central Nervous System Neoplasms ,0302 clinical medicine ,immune system diseases ,hemic and lymphatic diseases ,Tumor Microenvironment ,In Situ Hybridization, Fluorescence ,Aged, 80 and over ,CD68 ,General Medicine ,Middle Aged ,Prognosis ,3. Good health ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Female ,France ,Lymphoma, Large B-Cell, Diffuse ,Adult ,Primary central nervous system diffuse large B cell lymphoma ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Biology ,Pathology and Forensic Medicine ,03 medical and health sciences ,Lymphocytes, Tumor-Infiltrating ,Immune system ,PDL1 ,Biomarkers, Tumor ,medicine ,Humans ,Molecular Biology ,B cell ,Aged ,Retrospective Studies ,Tumour microenvironment ,Macrophages ,Cell Biology ,medicine.disease ,Immune checkpoint ,030104 developmental biology ,Immune checkpoints ,Cancer research ,PAX5 ,Diffuse large B-cell lymphoma ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,CD8 - Abstract
International audience; 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.
- Published
- 2019