title: Intratumoral macrophage phenotype and CD8+ T lymphocytes as potential tools to predict local tumor outgrowth at the intervention site in malignant pleural mesothelioma.
abstract: OBJECTIVE
  In patients with malignant pleural mesothelioma (MPM), local tumor outgrowth (LTO) after invasive procedures is a well-known complication. Currently, no biomarker is available to predict the occurrence of LTO. This study aims to investigate whether the tumor macrophage infiltration and phenotype of and/or the infiltration of CD8+ T-cells predicts LTO.
  
  
  METHODS
  Ten mesothelioma patients who developed LTO were clinically and pathologically matched with 10 non-LTO mesothelioma patients. Immunohistochemistry was performed on diagnostic biopsies to determine the total TAM (CD68), the M2 TAM (CD163) and CD8+ T-cell count (CD8).
  
  
  RESULTS
  The mean M2/total TAM ratio differed between the two groups: 0.90±0.09 in the LTO group versus 0.63±0.09 in patients without LTO (p<0.001). In addition, the mean CD8+ T-cell count was significantly different between the two groups: 30 per 0.025 cm2 (range 2-60) in the LTO group and 140 per 0.025 cm2 (range 23-314) in the patients without LTO (p<0.01).
  
  
  CONCLUSIONS
  This study shows that patients who develop LTO after a local intervention have a higher M2/total TAM ratio and lower CD8+ cell count at diagnosis compared to patients who did not develop this outgrowth. We propose that the M2/total TAM ratio and the CD8+ T-cell amount are potential tools to predict which MPM patients are prone to develop LTO.
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Robin
authors.initials: R
authors.lastname: Cornelissen
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Lysanne A
authors.initials: LA
authors.lastname: Lievense
authors.affiliation: Department of Pathology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Jan-Lukas
authors.initials: JL
authors.lastname: Robertus
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Rudi W
authors.initials: RW
authors.lastname: Hendriks
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Henk C
authors.initials: HC
authors.lastname: Hoogsteden
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
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. Electronic address: j.aerts@erasmusmc.nl.
authors.forename: Joachim G J V
authors.initials: JG
authors.lastname: Aerts
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015415:Biomarkers; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D002452:Cell Count; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality / Q000473:pathology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality / Q000473:pathology*; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D009367:Neoplasm Staging; D010641:Phenotype; D010997:Pleural Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers
keywords: Local tumor outgrowth; Macrophages; Mesothelioma; Prophylactic radiation of intervention tract; Tract metastases; Tumor micro-environment