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PD-1 and PD-L1 are upregulated in paired consecutive biopsies with classical Hodgkin lymphoma
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.ORCID iD: 0000-0002-0226-5681
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.ORCID iD: 0000-0002-0594-724x
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Abstract [en]

Background: High proportions of programmed death receptor 1 (PD-1) and its ligand (PD-L1) in the microenvironment of primary classical Hodgkin lymphoma (cHL) are associated with inferior outcome. However, it is unclear how expression alter during disease progression and if treatment and a subsequent relapse affect their expression. Our aim was to study the heterogeneity of PD-1 and PD-L1 in paired biopsies from untreated and treated cHL patients

Patients and methods: Patients with multiple biopsies with cHL were identified from three Swedish pathology departments. Eleven patients had a paired diagnostic cHL biopsy and a previous benign lymph node biopsy, which during our review were reclassified as cHL, designated as the untreated group. Thirty patients had a paired primary and a relapse biopsy, designated as the treated group. Cases were immunostained to detect PD-1+ and PD-L1+ leukocytes, and PD-L1+ Hodgkin and Reed-Sternberg (HRS) cells. Differences in expression between biopsies were tested using Wilcoxon signed rank test.

Results: In the untreated group, 8 of 11 cases (73%) showed an increased proportion of PD-L1+ leukocytes in biopsy 2 compared to biopsy 1, while none of the markers were statistically significantly different when biopsy 1 and 2 were compared. In the treated group, 19 of 30 (63%), 22 of 30 (73%), and 18 of 30 (60%) cases showed increased proportions of PD-1+ leukocytes, PD-L1+ leukocytes and PD-L1+ HRS cells, respectively. When the primary and the relapse biopsies were compared, PD-1+ leukocytes (p=0.04), PD-L1+ leukocytes (p=0.005) and PD-L1+ HRS cells (p=0.009) were statistically significantly different.   

Conclusion: Our findings indicate that PD-1 and PD-L1 increase both due to longer disease duration and following treatment in relapsed cHL.

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Cancer and Oncology
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URN: urn:nbn:se:uu:diva-336018OAI: oai:DiVA.org:uu-336018DiVA: diva2:1164762
Available from: 2017-12-11 Created: 2017-12-11 Last updated: 2017-12-14Bibliographically approved
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Hollander, PeterAmini, Rose-MarieEnblad, GunillaGlimelius, Ingrid

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