title: Precision immunotherapy; dynamics in the cellular profile of pleural effusions in malignant mesothelioma patients.
abstract: Clinical studies have proven the potential of immunotherapy in malignancies. To increase efficacy, a prerequisite is that treatment is tailored, so precision immune-oncology is the logical next step. In order to tailor treatment, characterization of the patient's tumor environment is key. Pleural effusion (PE) often accompanies malignant pleural mesothelioma (MPM) and is an important part of the MPM environment. Furthermore, the composition of PE is used as surrogate for the tumor. In this study, we provide an insight in the dynamics of the MPM environment through characterization of PE composition over time and show that the immunological characteristics of PE do not necessarily mirror those of the tumor.
  
  
  
  From 5 MPM patients, PE and tumor biopsies were acquired at the same time point. From one of these patients multiple PEs were obtained. PEs were acquired performing thoracocenteses and total cell amounts were determined. Immunohistochemistry was performed to quantify immune cell composition (T cells, macrophages) and tumor cells in PE derived cytospins and tumor biopsies.
  
  
  
  The PE amount and (immune) cellular composition varied considerably over time between multiple (n=10) thoracocenteses. These dynamics could in part be attributed to the treatment regimen consisting of standard chemotherapy and dendritic cell (DC)-based immunotherapy. In addition, the presence of T cells and macrophages in PE did not necessarily mirror the infiltration of these immune cells within tumor biopsies in 4 out of 5 patients.
  
  
  
  In this proof-of-concept study with limited sample size, we demonstrate that the composition of PE is dynamic and influenced by treatment. Furthermore, the immune cell composition of PE does not automatically reflect the properties of tumor tissue. This has major consequences when applying precision immunotherapy based on PE findings in patients. Furthermore, it implies a regulated trafficking of immune regulating cells within the tumor environment.
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC Cancer Institute, Rotterdam, The Netherlands. Electronic address: l.lievense@erasmusmc.nl.
authors.forename: Lysanne A
authors.initials: LA
authors.lastname: Lievense
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC Cancer Institute, Rotterdam, The Netherlands. Electronic address: k.bezemer@erasmusmc.nl.
authors.forename: Koen
authors.initials: K
authors.lastname: Bezemer
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC Cancer Institute, Rotterdam, The Netherlands. Electronic address: r.cornelissen@erasmusmc.nl.
authors.forename: Robin
authors.initials: R
authors.lastname: Cornelissen
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC Cancer Institute, Rotterdam, The Netherlands. Electronic address: m.lambers@erasmusmc.nla.
authors.forename: Margaretha E H
authors.initials: ME
authors.lastname: Kaijen-Lambers
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC Cancer Institute, Rotterdam, The Netherlands. Electronic address: j.hegmans@erasmusmc.nl.
authors.forename: Joost P J J
authors.initials: JP
authors.lastname: Hegmans
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC Cancer Institute, Rotterdam, The Netherlands; Department of Pulmonary Medicine, Amphia Hospital, Breda, The Netherlands. Electronic address: j.aerts@erasmusmc.nl.
authors.forename: Joachim G J V
authors.initials: JG
authors.lastname: Aerts
mesh_terms: D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008175:Lung Neoplasms / Q000150:complications / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism; D008654:Mesothelioma / Q000150:complications / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D000086002:Mesothelioma, Malignant; D016066:Pleural Effusion, Malignant / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D010997:Pleural Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D057285:Precision Medicine; D013601:T-Lymphocytes / Q000276:immunology; D000069258:Thoracentesis / Q000379:methods; D059016:Tumor Microenvironment / Q000276:immunology
keywords: Immunotherapy; Malignant mesothelioma; Pleural effusion; Tumor environment