Intratumoral macrophage phenotype and CD8+ T lymphocytes as potential tools to predict local tumor outgrowth at the intervention site in malignant pleural mesothelioma

Lung Cancer. 2015 Jun;88(3):332-7. doi: 10.1016/j.lungcan.2015.03.013. Epub 2015 Mar 21.

Abstract

Objectives: 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.

Materials and 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).

Conclusion: 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.

Keywords: Local tumor outgrowth; Macrophages; Mesothelioma; Prophylactic radiation of intervention tract; Tract metastases; Tumor micro-environment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology*
  • Cell Count
  • Female
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Macrophages / pathology*
  • Male
  • Mesothelioma / drug therapy
  • Mesothelioma / immunology*
  • Mesothelioma / mortality
  • Mesothelioma / pathology*
  • Mesothelioma, Malignant
  • Middle Aged
  • Neoplasm Staging
  • Phenotype
  • Pleural Neoplasms / drug therapy
  • Pleural Neoplasms / immunology*
  • Pleural Neoplasms / mortality
  • Pleural Neoplasms / pathology*
  • Prognosis
  • Tomography, X-Ray Computed
  • Treatment Outcome

Substances

  • Biomarkers