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PD-L1 expression is low in large B-cell lymphoma with MYC or double-hit translocation

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@article{2f9dc1b5e8f54fc394ee46f408b02e8b,
title = "PD-L1 expression is low in large B-cell lymphoma with MYC or double-hit translocation",
abstract = "In large B-cell lymphoma (LBCL), MYC translocation and MYC/BCL2 or MYC/BCL6 double hit (DH) are associated with poor prognosis, and there is an unmet need for novel treatment targets in this patient group. Treatments targeting the PD-L1/PD-1 pathway are still poorly elucidated in LBCL. PD-L1 expression might predict response to treatment targeting the PD-L1/PD-1 pathway. We therefore investigated the relationship between PD-L1 protein and mRNA expression levels and MYC and DH translocation in LBCL. We detected MYC, BCL2, and BCL6 translocation by fluorescent in situ hybridization in tissue samples from 130 patients randomly selected from two cohorts of patients with LBCL: 49 patients with MYC translocation of whom 36 had DH and 81 without MYC translocation. PD-L1 protein expression was detected by immunohistochemistry (IHC) in tissue samples from 77 patients and PD-L1 mRNA expression by next-generation RNA sequencing (NGS) in another 77 patients. Twenty-four patients overlapped, ie, were analysed with both IHC and NGS. Nonparametric tests were performed to evaluate intergroup differences. PD-L1 protein expression level was significantly lower in patients with MYC (n = 42, median = 3.3{\%}, interquartile range [IQR] 0.0-10.8) or DH translocations (n = 31, median = 3.3{\%}, IQR 0.0-10.0) compared with patients with no MYC (n = 35, median = 16.7{\%}, IQR 3.3-30.0) or no DH translocations (n = 46, 13.3{\%}, IQR 2.5-30.0), P = .004 and P ≤ .001, respectively. PD-L1 mRNA expression was also significantly lower in patients with MYC or DH translocations, P = .001 and P = .006, respectively. Higher PD-L1 protein and mRNA expression levels were associated with non-germinal centre (GC) type compared with germinal centre B-cell (GCB)-type diffuse LBCL (DLBCL), P = .004 and P = .002, respectively. In conclusion, we report an association between low PD-L1 expression and MYC and DH translocation in patients with LBCL. Our findings may indicate that patients with MYC or DH translocation may benefit less from treatment with PD-L1/PD-1-inhibitors compared with patients without these translocations. This should be evaluated in larger, prospective, consecutive trials.",
keywords = "Adult, Aged, B-Lymphocyte Subsets/metabolism, B7-H1 Antigen/biosynthesis, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genes, bcl-2, Genes, myc, Germinal Center/pathology, High-Throughput Nucleotide Sequencing, Humans, Lymphoma, Large B-Cell, Diffuse/metabolism, Male, Middle Aged, Neoplasm Proteins/biosynthesis, Neoplastic Stem Cells/metabolism, Proto-Oncogene Proteins c-bcl-6/genetics, RNA, Messenger/biosynthesis, RNA, Neoplasm/biosynthesis, Retrospective Studies, Translocation, Genetic",
author = "Elbaek, {Mette Vestergaard} and Pedersen, {Mette {\O}lgod} and Breinholt, {Marie Fredslund} and Anupama Reddy and Cassandra Love and Erik Clasen-Linde and Helle Knudsen and Nielsen, {Signe Ledou} and Gang, {Anne Ortved} and Estrid H{\o}gdall and Sandeep Dave and Peter N{\o}rgaard",
note = "{\circledC} 2019 John Wiley & Sons, Ltd.",
year = "2019",
month = "10",
doi = "10.1002/hon.2664",
language = "English",
volume = "37",
pages = "375--382",
journal = "Hematology / Oncology Clinics of North America",
issn = "0889-8588",
publisher = "W.B./Saunders Co",
number = "4",

}

RIS

TY - JOUR

T1 - PD-L1 expression is low in large B-cell lymphoma with MYC or double-hit translocation

AU - Elbaek, Mette Vestergaard

AU - Pedersen, Mette Ølgod

AU - Breinholt, Marie Fredslund

AU - Reddy, Anupama

AU - Love, Cassandra

AU - Clasen-Linde, Erik

AU - Knudsen, Helle

AU - Nielsen, Signe Ledou

AU - Gang, Anne Ortved

AU - Høgdall, Estrid

AU - Dave, Sandeep

AU - Nørgaard, Peter

N1 - © 2019 John Wiley & Sons, Ltd.

PY - 2019/10

Y1 - 2019/10

N2 - In large B-cell lymphoma (LBCL), MYC translocation and MYC/BCL2 or MYC/BCL6 double hit (DH) are associated with poor prognosis, and there is an unmet need for novel treatment targets in this patient group. Treatments targeting the PD-L1/PD-1 pathway are still poorly elucidated in LBCL. PD-L1 expression might predict response to treatment targeting the PD-L1/PD-1 pathway. We therefore investigated the relationship between PD-L1 protein and mRNA expression levels and MYC and DH translocation in LBCL. We detected MYC, BCL2, and BCL6 translocation by fluorescent in situ hybridization in tissue samples from 130 patients randomly selected from two cohorts of patients with LBCL: 49 patients with MYC translocation of whom 36 had DH and 81 without MYC translocation. PD-L1 protein expression was detected by immunohistochemistry (IHC) in tissue samples from 77 patients and PD-L1 mRNA expression by next-generation RNA sequencing (NGS) in another 77 patients. Twenty-four patients overlapped, ie, were analysed with both IHC and NGS. Nonparametric tests were performed to evaluate intergroup differences. PD-L1 protein expression level was significantly lower in patients with MYC (n = 42, median = 3.3%, interquartile range [IQR] 0.0-10.8) or DH translocations (n = 31, median = 3.3%, IQR 0.0-10.0) compared with patients with no MYC (n = 35, median = 16.7%, IQR 3.3-30.0) or no DH translocations (n = 46, 13.3%, IQR 2.5-30.0), P = .004 and P ≤ .001, respectively. PD-L1 mRNA expression was also significantly lower in patients with MYC or DH translocations, P = .001 and P = .006, respectively. Higher PD-L1 protein and mRNA expression levels were associated with non-germinal centre (GC) type compared with germinal centre B-cell (GCB)-type diffuse LBCL (DLBCL), P = .004 and P = .002, respectively. In conclusion, we report an association between low PD-L1 expression and MYC and DH translocation in patients with LBCL. Our findings may indicate that patients with MYC or DH translocation may benefit less from treatment with PD-L1/PD-1-inhibitors compared with patients without these translocations. This should be evaluated in larger, prospective, consecutive trials.

AB - In large B-cell lymphoma (LBCL), MYC translocation and MYC/BCL2 or MYC/BCL6 double hit (DH) are associated with poor prognosis, and there is an unmet need for novel treatment targets in this patient group. Treatments targeting the PD-L1/PD-1 pathway are still poorly elucidated in LBCL. PD-L1 expression might predict response to treatment targeting the PD-L1/PD-1 pathway. We therefore investigated the relationship between PD-L1 protein and mRNA expression levels and MYC and DH translocation in LBCL. We detected MYC, BCL2, and BCL6 translocation by fluorescent in situ hybridization in tissue samples from 130 patients randomly selected from two cohorts of patients with LBCL: 49 patients with MYC translocation of whom 36 had DH and 81 without MYC translocation. PD-L1 protein expression was detected by immunohistochemistry (IHC) in tissue samples from 77 patients and PD-L1 mRNA expression by next-generation RNA sequencing (NGS) in another 77 patients. Twenty-four patients overlapped, ie, were analysed with both IHC and NGS. Nonparametric tests were performed to evaluate intergroup differences. PD-L1 protein expression level was significantly lower in patients with MYC (n = 42, median = 3.3%, interquartile range [IQR] 0.0-10.8) or DH translocations (n = 31, median = 3.3%, IQR 0.0-10.0) compared with patients with no MYC (n = 35, median = 16.7%, IQR 3.3-30.0) or no DH translocations (n = 46, 13.3%, IQR 2.5-30.0), P = .004 and P ≤ .001, respectively. PD-L1 mRNA expression was also significantly lower in patients with MYC or DH translocations, P = .001 and P = .006, respectively. Higher PD-L1 protein and mRNA expression levels were associated with non-germinal centre (GC) type compared with germinal centre B-cell (GCB)-type diffuse LBCL (DLBCL), P = .004 and P = .002, respectively. In conclusion, we report an association between low PD-L1 expression and MYC and DH translocation in patients with LBCL. Our findings may indicate that patients with MYC or DH translocation may benefit less from treatment with PD-L1/PD-1-inhibitors compared with patients without these translocations. This should be evaluated in larger, prospective, consecutive trials.

KW - Adult

KW - Aged

KW - B-Lymphocyte Subsets/metabolism

KW - B7-H1 Antigen/biosynthesis

KW - Female

KW - Gene Expression Profiling

KW - Gene Expression Regulation, Neoplastic

KW - Genes, bcl-2

KW - Genes, myc

KW - Germinal Center/pathology

KW - High-Throughput Nucleotide Sequencing

KW - Humans

KW - Lymphoma, Large B-Cell, Diffuse/metabolism

KW - Male

KW - Middle Aged

KW - Neoplasm Proteins/biosynthesis

KW - Neoplastic Stem Cells/metabolism

KW - Proto-Oncogene Proteins c-bcl-6/genetics

KW - RNA, Messenger/biosynthesis

KW - RNA, Neoplasm/biosynthesis

KW - Retrospective Studies

KW - Translocation, Genetic

U2 - 10.1002/hon.2664

DO - 10.1002/hon.2664

M3 - Journal article

VL - 37

SP - 375

EP - 382

JO - Hematology / Oncology Clinics of North America

JF - Hematology / Oncology Clinics of North America

SN - 0889-8588

IS - 4

ER -

ID: 59043532