Ratio of intratumoral macrophage phenotypes is a prognostic factor in epithelioid malignant pleural mesothelioma

PLoS One. 2014 Sep 5;9(9):e106742. doi: 10.1371/journal.pone.0106742. eCollection 2014.

Abstract

Hypothesis: The tumor micro-environment and especially the different macrophage phenotypes appear to be of great influence on the behavior of multiple tumor types. M1 skewed macrophages possess anti-tumoral capacities, while the M2 polarized macrophages have pro-tumoral capacities. We analyzed if the macrophage count and the M2 to total macrophage ratio is a discriminative marker for outcome after surgery in malignant pleural mesothelioma (MPM) and studied the prognostic value of these immunological cells.

Methods: 8 MPM patients who received induction chemotherapy and surgical treatment were matched on age, sex, tumor histology, TNM stage and EORTC score with 8 patients who received chemotherapy only. CD8 positive T-cells and the total macrophage count, using the CD68 pan-macrophage marker, and CD163 positive M2 macrophage count were determined in tumor specimens prior to treatment.

Results: The number of CD68 and CD163 cells was comparable between the surgery and the non-surgery group, and was not related to overall survival (OS) in both the surgery and non-surgery group. However, the CD163/CD68 ratio did correlate with OS in both in the total patient group (Pearson r -0.72, p<0.05). No correlation between the number of CD8 cells and prognosis was found.

Conclusions: The total number of macrophages in tumor tissue did not correlate with OS in both groups, however, the CD163/CD68 ratio correlates with OS in the total patient group. Our data revealed that the CD163/CD68 ratio is a potential prognostic marker in epithelioid mesothelioma patients independent of treatment but cannot be used as a predictive marker for outcome after surgery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Antigens, Surface / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / pathology
  • Female
  • Humans
  • Lung Neoplasms / immunology
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Macrophages / pathology
  • Male
  • Mesothelioma / immunology
  • Mesothelioma / metabolism*
  • Mesothelioma / mortality
  • Mesothelioma / pathology*
  • Mesothelioma, Malignant
  • Middle Aged
  • Neoplasm Staging
  • Phenotype*
  • Pleural Neoplasms / immunology
  • Pleural Neoplasms / metabolism*
  • Pleural Neoplasms / mortality
  • Pleural Neoplasms / pathology*
  • Prognosis
  • Receptors, Cell Surface / metabolism
  • Tumor Microenvironment

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Antigens, Surface
  • CD163 antigen
  • CD68 antigen, human
  • Receptors, Cell Surface

Grants and funding

Stichting Asbestkanker Rotterdam, Mesothelioma Applied Research Foundation (MARF) – Larry Davis Memorial Grant. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.