PD-L1 and IDO1 are potential targets for treatment in patients with primary diffuse large B-cell lymphoma of the CNS. (3rd April 2021)

• Record Type: Journal Article
• Authors: Abdulla, Maysaa; Alexsson, Andrei; Sundström, Christer; Ladenvall, Claes; Mansouri, Larry; Lindskog, Cecilia; Berglund, Mattias; Cavelier, Lucia; Enblad, Gunilla; Hollander, Peter; Amini, Rose-Marie
• Is Part Of: Acta oncologica. Volume 60:Number 4(2021)
• Page Start: 531
• Page End: 538
• Publication Date: 2021-04-03
• Subjects: PCNSL -- PD-1 -- PD-L1 -- PD-L2 -- IDO1 -- EBER; Oncology -- Periodicals; Cancer -- Treatment -- Periodicals; 616.992
• DOI: 10.1080/0284186X.2021.1881161
• Languages: English
• ISSNs: 0284-186X

Abstract

Abstract: Background: Programmed cell death 1 (PD-1) and its ligands PD-L1 and PD-L2, as well as Indoleamine 2, 3-deoxygenase (IDO1) can be expressed both by tumor and microenvironmental cells and are crucial for tumor immune escape. We aimed to evaluate the role of PD-1, its ligands and IDO1 in a cohort of patients with primary diffuse large B-cell lymphoma of the CNS (PCNSL). Material and methods: Tissue microarrays (TMAs) were constructed in 45 PCNSL cases. RNA extraction from whole tissue sections and RNA sequencing were successfully performed in 33 cases. Immunohistochemical stainings for PD-1, PD-L1/paired box protein 5 (PAX-5), PD-L2/PAX-5 and IDO1, and Epstein-Barr virus encoding RNA (EBER) in situ hybridization were analyzed. Results: High proportions of PD-L1 and PD-L2 positive tumor cells were observed in 11% and 9% of cases, respectively. High proportions of PD-L1 and PD-L2 positive leukocytes were observed in 55% and 51% of cases, respectively. RNA sequencing revealed that gene expression of IDO1 was high in patients with high proportion of PD-L1 positive leukocytes ( p = .01). Protein expression of IDO1 in leukocytes was detected in 14/45 cases, in 79% of these cases a high proportion of PD-L1 positive leukocytes was observed. Gene expression of IDO1 was high in EBER-positive cases ( p = .0009) and protein expression of IDO1 was detected in five of six EBER-positive cases. Conclusion: Our study shows a significant association between gene and protein expression of IDO1 and protein expression of PD-L1 in the tumor microenvironment of PCNSL, possibly of importance for prediction of response to immunotherapies.