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Leukemia & Lymphoma Volume 60, 2019 - Issue 2
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Original Article: Research

Expression of PD-1, PD-L1, and PD-L2 in posttransplant lymphoproliferative disorder after solid organ transplantation

Amelie Kincha Department of Medical Sciences, Section of Infectious Diseases, Uppsala University, Uppsala, Sweden; Correspondence[email protected]
ORCID Iconhttps://orcid.org/0000-0003-3420-8590
ORCID Icon,
Christer Sundströmb Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden;
,
Eva Baecklundc Department of Medical Sciences, Section of Rheumatology, Uppsala University, Uppsala, Sweden;
,
Carin Backlinc Department of Medical Sciences, Section of Rheumatology, Uppsala University, Uppsala, Sweden; ;d Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden;
,
Daniel Moline Experimental and Clinical Oncology, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
&
Gunilla Enblade Experimental and Clinical Oncology, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, SwedenORCID Iconhttps://orcid.org/0000-0002-0594-724X
ORCID Icon
Pages 376-384 | Received 12 Jan 2018, Accepted 07 May 2018, Published online: 22 Jul 2018

Figures & data

Table 1. Associations between the expression of PD-1, PD-L1, and PD-L2 in PTLD tissue, PTLD subtype, and clinical features.

Figure 1. Proportion of PTLDs positive for PD-1 in tumor-infiltrating cells (A) and for PD-L1 and PD-L2 in tumor cells (B).

Figure 1. Proportion of PTLDs positive for PD-1 in tumor-infiltrating cells (A) and for PD-L1 and PD-L2 in tumor cells (B).

Figure 2. Expression of PD-1, -L1, and -L2 by subtype and EBV-status of PTLD.

PTLD: posttransplant lymphoproliferative disorder; EBER: Epstein–Barr virus-encoded RNA; LMP1: latent membrane protein 1; PD-1: programed death protein 1; PD-L1: programed death ligand 1; PD-L2: programed death ligand 2; H: heart; K: kidney; LU: lung; P: pancreas; LI: liver; DLBCL: diffuse large B-cell lymphoma; NGC: non-germinal center; GC: germinal center; Aggressive B: aggressive B-cell lymphoma, unclassifiable; Aggressive T: aggressive T-cell lymphoma, unclassifiable; ALCL: anaplastic large cell lymphoma; EATL: enteropathy-associated T-cell lymphoma; HSTL: hepatosplenic T-cell lymphoma; LBTL: lymphoblastic lymphoma; PTCL-NOS: peripheral T-cell lymphoma, unspecified; L-UNC: lymphoma, unclassifiable; +: positive; –: negative; MD: missing data.

Figure 2. Expression of PD-1, -L1, and -L2 by subtype and EBV-status of PTLD.PTLD: posttransplant lymphoproliferative disorder; EBER: Epstein–Barr virus-encoded RNA; LMP1: latent membrane protein 1; PD-1: programed death protein 1; PD-L1: programed death ligand 1; PD-L2: programed death ligand 2; H: heart; K: kidney; LU: lung; P: pancreas; LI: liver; DLBCL: diffuse large B-cell lymphoma; NGC: non-germinal center; GC: germinal center; Aggressive B: aggressive B-cell lymphoma, unclassifiable; Aggressive T: aggressive T-cell lymphoma, unclassifiable; ALCL: anaplastic large cell lymphoma; EATL: enteropathy-associated T-cell lymphoma; HSTL: hepatosplenic T-cell lymphoma; LBTL: lymphoblastic lymphoma; PTCL-NOS: peripheral T-cell lymphoma, unspecified; L-UNC: lymphoma, unclassifiable; +: positive; –: negative; MD: missing data.

Figure 3. Immunohistochemical stainings of PD-1, PD-L1, and PD-L2 in PTLD. First row: Anaplastic large cell lymphoma (ALCL) positive in all three stainings, with a membranous staining pattern for PD-1(A) and PD-L1 (B), and a cytoplasmic and nuclear pattern for PD-L2 (C); Second row: Diffuse large B-cell lymphoma (DLBCL) of non-germinal center (non-GC) type with a membranous staining pattern for PD-1 (D) and PD-L1 (E), but negative for PD-L2 (F); Third row: DLBCL of GC type positive for PD-1 in a membranous pattern (G), with <5% of the tumor cells positive for PD-L1, therefore regarded as PD-L1 negative (H), but PD-L2 positive in a cytoplasmic and nuclear pattern (I); Fourth row: DLBCL of non-GC type negative for PD-1 (J), but positive for PD-L1 in a membranous (K) and PD-L2 in a cytoplasmic pattern (L).

Figure 3. Immunohistochemical stainings of PD-1, PD-L1, and PD-L2 in PTLD. First row: Anaplastic large cell lymphoma (ALCL) positive in all three stainings, with a membranous staining pattern for PD-1(A) and PD-L1 (B), and a cytoplasmic and nuclear pattern for PD-L2 (C); Second row: Diffuse large B-cell lymphoma (DLBCL) of non-germinal center (non-GC) type with a membranous staining pattern for PD-1 (D) and PD-L1 (E), but negative for PD-L2 (F); Third row: DLBCL of GC type positive for PD-1 in a membranous pattern (G), with <5% of the tumor cells positive for PD-L1, therefore regarded as PD-L1 negative (H), but PD-L2 positive in a cytoplasmic and nuclear pattern (I); Fourth row: DLBCL of non-GC type negative for PD-1 (J), but positive for PD-L1 in a membranous (K) and PD-L2 in a cytoplasmic pattern (L).

Table 2. Expression of PD-1, PD-L1, and PD-L2 in PTLD tissue.

Table 3. Combinations of expression of PD-1, PD-L1, and PD-L2 by subtype and EBV-status of PTLD.

Related Research Data

Checkpoint Inhibitors in Kidney Transplant Recipients and the Potential Risk of Rejection
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B-Cell and Classical Hodgkin Lymphomas Associated With Immunodeficiency: 2015 SH/EAHP Workshop Report-Part 2.
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The 2016 revision of the World Health Organization classification of lymphoid neoplasms
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Tumor Regression and Allograft Rejection after Administration of Anti–PD-1
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Epstein Barr Virus Associated B-Cell Lymphomas and Iatrogenic Lymphoproliferative Disorders.
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A population-based study of 135 lymphomas after solid organ transplantation: The role of Epstein-Barr virus, hepatitis C and diffuse large B-cell lymphoma subtype in clinical presentation and survival.
Source: Informa UK Limited
PD-L1 and PD1 expression in post-transplantation lymphoproliferative disease (PTLD) of childhood and adolescence: An inter- and intra-individual descriptive study covering the whole spectrum of PTLD categories.
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Constitutive AP-1 Activity and EBV Infection Induce PD-L1 in Hodgkin Lymphomas and Posttransplant Lymphoproliferative Disorders: Implications for Targeted Therapy
Source: American Association for Cancer Research (AACR)
Antitumor activity of nivolumab on hemodialysis after renal allograft rejection.
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