Prognostic Role of Tumor Immune Microenvironment in Pleural Epithelioid Mesothelioma

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http://hdl.handle.net/10138/346406

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Ollila , H , Mäyranpää , M I , Paavolainen , L , Paajanen , J , Välimäki , K , Sutinen , E , Wolff , H , Räsänen , J , Kallioniemi , O , Myllärniemi , M , Ilonen , I & Pellinen , T 2022 , ' Prognostic Role of Tumor Immune Microenvironment in Pleural Epithelioid Mesothelioma ' , Frontiers in oncology , vol. 12 , 870352 . https://doi.org/10.3389/fonc.2022.870352

Title: Prognostic Role of Tumor Immune Microenvironment in Pleural Epithelioid Mesothelioma
Author: Ollila, Hely; Mäyranpää, Mikko I.; Paavolainen, Lassi; Paajanen, Juuso; Välimäki, Katja; Sutinen, Eva; Wolff, Henrik; Räsänen, Jari; Kallioniemi, Olli; Myllärniemi, Marjukka; Ilonen, Ilkka; Pellinen, Teijo
Contributor organization: University of Helsinki
INDIVIDRUG - Individualized Drug Therapy
HUS Heart and Lung Center
Keuhkosairauksien yksikkö
HUSLAB
Department of Pathology
Bioimage Profiling
Institute for Molecular Medicine Finland
Precision Systems Medicine
Department of Medicine
Medicum
III kirurgian klinikka
Clinicum
Department of Surgery
Helsinki Institute of Life Science HiLIFE
Date: 2022-06-20
Language: eng
Number of pages: 10
Belongs to series: Frontiers in oncology
ISSN: 2234-943X
DOI: https://doi.org/10.3389/fonc.2022.870352
URI: http://hdl.handle.net/10138/346406
Abstract: BackgroundPleural mesothelioma (MPM) is an aggressive malignancy with an average patient survival of only 10 months. Interestingly, about 5%-10% of the patients survive remarkably longer. Prior studies have suggested that the tumor immune microenvironment (TIME) has potential prognostic value in MPM. We hypothesized that high-resolution single-cell spatial profiling of the TIME would make it possible to identify subpopulations of patients with long survival and identify immunophenotypes for the development of novel treatment strategies. MethodsWe used multiplexed fluorescence immunohistochemistry (mfIHC) and cell-based image analysis to define spatial TIME immunophenotypes in 69 patients with epithelioid MPM (20 patients surviving >= 36 months). Five mfIHC panels (altogether 21 antibodies) were used to classify tumor-associated stromal cells and different immune cell populations. Prognostic associations were evaluated using univariate and multivariable Cox regression, as well as combination risk models with area under receiver operating characteristic curve (AUROC) analyses. ResultsWe observed that type M2 pro-tumorigenic macrophages (CD163(+)pSTAT1(-)HLA-DRA1(-)) were independently associated with shorter survival, whereas granzyme B+ cells and CD11c(+) cells were independently associated with longer survival. CD11c(+) cells were the only immunophenotype increasing the AUROC (from 0.67 to 0.84) when added to clinical factors (age, gender, clinical stage, and grade). ConclusionHigh-resolution, deep profiling of TIME in MPM defined subgroups associated with both poor (M2 macrophages) and favorable (granzyme B/CD11c positivity) patient survival. CD11c positivity stood out as the most potential prognostic cell subtype adding prediction power to the clinical factors. These findings help to understand the critical determinants of TIME for risk and therapeutic stratification purposes in MPM.
Subject: pleural mesothelioma
tumor immune microenvironment
multiplexed fluorescence immunohistochemistry
prognosis
dendritic cells
GRANZYME-B
CELLS
SURVIVAL
3122 Cancers
3126 Surgery, anesthesiology, intensive care, radiology
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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