PD-L1(+) tumor-associated macrophages and PD-1(+) tumor-infiltrating lymphocytes predict survival in primary testicular lymphoma

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dc.contributor University of Helsinki, University of Helsinki en
dc.contributor University of Helsinki, Department of Clinical Chemistry and Hematology en
dc.contributor University of Helsinki, Institute for Molecular Medicine Finland en
dc.contributor University of Helsinki, Department of Oncology en
dc.contributor University of Helsinki, Medicum en
dc.contributor University of Helsinki, Sirpa Marianne Leppä / Principal Investigator en
dc.contributor University of Helsinki, Institute for Molecular Medicine Finland en
dc.contributor University of Helsinki, Department of Clinical Chemistry and Hematology en
dc.contributor University of Helsinki, Research Programs Unit en
dc.contributor University of Helsinki, Department of Oncology en
dc.contributor.author Pollari, Marjukka
dc.contributor.author Brück, Oscar
dc.contributor.author Pellinen, Teijo
dc.contributor.author Vähämurto, Pauli
dc.contributor.author Karjalainen-Lindsberg, Marja-Liisa
dc.contributor.author Mannisto, Susanna
dc.contributor.author Kallioniemi, Olli
dc.contributor.author Kellokumpu-Lehtinen, Pirkko-Liisa
dc.contributor.author Mustjoki, Satu
dc.contributor.author Leivonen, Suvi-Katri
dc.contributor.author Leppä, Sirpa
dc.date.accessioned 2018-12-20T14:02:01Z
dc.date.available 2018-12-20T14:02:01Z
dc.date.issued 2018-10-31
dc.identifier.citation Pollari , M , Brück , O , Pellinen , T , Vähämurto , P , Karjalainen-Lindsberg , M-L , Mannisto , S , Kallioniemi , O , Kellokumpu-Lehtinen , P-L , Mustjoki , S , Leivonen , S-K & Leppä , S 2018 , ' PD-L1(+) tumor-associated macrophages and PD-1(+) tumor-infiltrating lymphocytes predict survival in primary testicular lymphoma ' , Haematologica , vol. 103 , no. 11 , pp. 1908-1914 . https://doi.org/10.3324/haematol.2018.197194 en
dc.identifier.issn 0390-6078
dc.identifier.other PURE: 120365794
dc.identifier.other PURE UUID: 52c66534-eb08-4f10-9b85-a1739251ecdb
dc.identifier.other WOS: 000451732200034
dc.identifier.other ORCID: /0000-0002-8265-511X/work/51990165
dc.identifier.other ORCID: /0000-0003-3224-0757/work/51990785
dc.identifier.other ORCID: /0000-0002-0816-8241/work/51991285
dc.identifier.other Scopus: 85055822642
dc.identifier.uri http://hdl.handle.net/10138/278905
dc.description.abstract Primary testicular lymphoma is a rare and aggressive lymphoid malignancy, most often representing diffuse large B-cell lymphoma histologically. Tumor-associated macrophages and tumor-infiltrating lymphocytes have been associated with survival in diffuse large B-cell lymphoma, but their prognostic impact in primary testicular lymphoma is unknown. Here, we aimed to identify macrophages, their immunophenotypes and association with lymphocytes, and translate the findings into survival of patients with primary testicular lymphoma. We collected clinical data and tumor tissue from 74 primary testicular lymphoma patients, and used multiplex immunohistochemistry and digital image analysis to examine macrophage markers (CD68, CD163, and c-Maf), T-cell markers (CD3, CD4, and CD8), B-cell marker (CD20), and three checkpoint molecules (PD-L1, PD-L2, and PD-1). We demonstrate that a large proportion of macrophages (median 41%, range 0.08-99%) and lymphoma cells (median 34%, range 0.1-100%) express PD-L1. The quantity of PD-L1+CD68+ macrophages correlates positively with the amount of PD-1+ lymphocytes, and a high proportion of either PD-L1+CD68+ macrophages or PD-1+CD4+ and PD-1+CD8+ T-cells translates into favorable survival. In contrast, the number of PD-L1+ lymphoma cells or PD-L1- macrophages do not associate with outcome. In multivariate analyses with IPI, PD-L1+CD68+ macrophage and PD-1+ lymphocyte contents remain as independent prognostic factors for survival. In conclusion, high PD-L1+CD68+ macrophage and PD-1+ lymphocyte contents predict favorable survival in patients with primary testicular lymphoma. The findings implicate that the tumor microenvironment and PD-1. PD-L1 pathway have a significant role in regulating treatment outcome. They also bring new insights to the targeted therapy of primary testicular lymphoma. en
dc.format.extent 7
dc.language.iso eng
dc.relation.ispartof Haematologica
dc.rights en
dc.subject B-CELL LYMPHOMA en
dc.subject CENTRAL-NERVOUS-SYSTEM en
dc.subject DEATH LIGAND 1 en
dc.subject CONTRALATERAL TESTIS en
dc.subject EXPRESSION en
dc.subject BLOCKADE en
dc.subject IRRADIATION en
dc.subject FEATURES en
dc.subject 3122 Cancers en
dc.title PD-L1(+) tumor-associated macrophages and PD-1(+) tumor-infiltrating lymphocytes predict survival in primary testicular lymphoma en
dc.type Article
dc.description.version Peer reviewed
dc.identifier.doi https://doi.org/10.3324/haematol.2018.197194
dc.type.uri info:eu-repo/semantics/other
dc.type.uri info:eu-repo/semantics/acceptedVersion
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