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Precursor cells and implications of a T-cell inflamed immune response in the pre-malignant setting in Hodgkin lymphoma.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology. (Rose-Marie Amini)ORCID iD: 0000-0002-0226-5681
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2019 (English)In: Immunobiology, ISSN 0171-2985, E-ISSN 1878-3279, article id S0171-2985(19)30248-7Article in journal (Refereed) Epub ahead of print
Abstract [en]

The etiology of classical Hodgkin lymphoma (cHL) is largely unknown. High serum CD30-levels are associated with increased risk of cHL. Epstein-Barr virus (EBV) is detectable in the tumor cells in 1/3 of cHL cases in the Western world. The PD-1 pathway (T-cell inflamed immune response) might contribute to the pathogenesis by enabling pre-malignant CD30+ or EBV + cells to evade immune surveillance. We aimed to investigate if high infiltrations of CD30+, PD-1+, PD-L1+ and EBV + cells in benign lymph nodes from patients that later develop cHL (cases) (n = 15) were associated with risk of cHL compared to controls (n = 45) with benign lymph nodes from patients that did not develop cHL. Pathology registries including 3500 cH L patients were screened. Lymph nodes were stained with immunohistochemistry and in situ hybridization and the risk for cHL calculated with logistic regression. High CD30-expression by B- and T-cells was associated with a decreased risk of cHL [(OR = 0.10, 95 % CI:0.03-0.39) and (OR = 0.13, 95 % CI:0.01-0.71), respectively], which remained significant for CD30 + B-cells (OR = 0.15, 95 % CI:0.03-0.60) in multivariate analyses. Amount of PD-1+, PD-L1+ and EBV + cells were not statistically significantly associated with risk of cHL. However, the amount of PD-L1+ leukocytes tended to be higher in cases later developing cHL (OR = 2.84, 95 % CI:0.61-12.61). High proportions of potential precursors to cHL, i.e. CD30 + B-cells in benign lymph nodes are not associated with an increased risk of cHL, while a tendency for a T-cell inflamed immune response, i.e. abundant PD-L1+ cells, was observed in biopsies taken prior to the cHL diagnosis.

Place, publisher, year, edition, pages
2019. article id S0171-2985(19)30248-7
Keywords [en]
CD30, EBV, Hodgkin lymphoma, PD-1, PD-L1, Pathogenesis
National Category
Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
URN: urn:nbn:se:uu:diva-400948DOI: 10.1016/j.imbio.2019.11.007PubMedID: 31787352OAI: oai:DiVA.org:uu-400948DiVA, id: diva2:1382647
Available from: 2020-01-03 Created: 2020-01-03 Last updated: 2020-01-03

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