Prognostic Impact of Tumor-Associated Macrophages on Survival Is Checkpoint Dependent in Classical Hodgkin Lymphoma

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http://hdl.handle.net/10138/316153

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Karihtala , K , Leivonen , S-K , Brück , O , Karjalainen-Lindsberg , M-L , Mustjoki , S , Pellinen , T & Leppä , S 2020 , ' Prognostic Impact of Tumor-Associated Macrophages on Survival Is Checkpoint Dependent in Classical Hodgkin Lymphoma ' , Cancers , vol. 12 , no. 4 , 877 . https://doi.org/10.3390/cancers12040877

Title: Prognostic Impact of Tumor-Associated Macrophages on Survival Is Checkpoint Dependent in Classical Hodgkin Lymphoma
Author: Karihtala, Kristiina; Leivonen, Suvi-Katri; Brück, Oscar; Karjalainen-Lindsberg, Marja-Liisa; Mustjoki, Satu; Pellinen, Teijo; Leppä, Sirpa
Contributor organization: ATG - Applied Tumor Genomics
Faculty of Medicine
University of Helsinki
Department of Oncology
HUS Comprehensive Cancer Center
Helsinki University Hospital Area
Research Programs Unit
Department of Clinical Chemistry and Hematology
TRIMM - Translational Immunology Research Program
Medicum
Department of Pathology
Hematologian yksikkö
Institute for Molecular Medicine Finland
Precision Systems Medicine
Date: 2020-04
Language: eng
Number of pages: 15
Belongs to series: Cancers
ISSN: 2072-6694
DOI: https://doi.org/10.3390/cancers12040877
URI: http://hdl.handle.net/10138/316153
Abstract: Tumor microenvironment and immune escape affect pathogenesis and survival in classical Hodgkin lymphoma (cHL). While tumor-associated macrophage (TAM) content has been associated with poor outcomes, macrophage-derived determinants with clinical impact have remained undefined. Here, we have used multiplex immunohistochemistry and digital image analysis to characterize TAM immunophenotypes with regard to expression of checkpoint molecules programmed cell death ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO-1) from the diagnostic tumor tissue samples of 130 cHL patients, and correlated the findings with clinical characteristics and survival. We show that a large proportion of TAMs express PD-L1 (CD68(+), median 32%; M2 type CD163(+), median 22%), whereas the proportion of TAMs expressing IDO-1 is lower (CD68(+), median 5.5%; CD163(+), median 1.4%). A high proportion of PD-L1 and IDO-1 expressing TAMs from all TAMs (CD68(+)), or from CD163(+) TAMs, is associated with inferior outcome. In multivariate analysis with age and stage, high proportions of PD-L1(+) and IDO-1(+) TAMs remain independent prognostic factors for freedom from treatment failure (PD-L1(+)CD68(+)/CD68(+), HR = 2.63, 95% CI 1.17-5.88, p = 0.019; IDO-1(+)CD68(+)/CD68(+), HR = 2.48, 95% CI 1.03-5.95, p = 0.042). In contrast, proportions of PD-L1(+) tumor cells, all TAMs or PD-L1(-) and IDO-1(-) TAMs are not associated with outcome. The findings implicate that adverse prognostic impact of TAMs is checkpoint-dependent in cHL.
Subject: classical hodgkin lymphoma
tumor-associated macrophages
tumor microenvironment
checkpoint molecules
multiplex immunohistochemistry
survival
INFILTRATING MACROPHAGES
BRENTUXIMAB VEDOTIN
IMMUNE EVASION
MICROENVIRONMENT
EXPRESSION
CELLS
PEMBROLIZUMAB
NIVOLUMAB
PATHWAYS
BLOCKADE
3122 Cancers
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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