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

• Published in: PloS one Vol. 9; no. 9; p. e106742
• Main Authors: Cornelissen, Robin, Lievense, Lysanne A, Maat, Alexander P, Hendriks, Rudi W, Hoogsteden, Henk C, Bogers, Ad J, Hegmans, Joost P, Aerts, Joachim G
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 05.09.2014; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Antigens, CD - metabolism; Antigens, Differentiation, Myelomonocytic - metabolism; Antigens, Surface - metabolism; Asbestos; Biology and Life Sciences; Cancer therapies; CD163 antigen; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - pathology; Chemotherapy; Clinical trials; Correlation; Female; Gene expression; Genotype & phenotype; Growth factors; Histology; Humans; Immunology; Lung Neoplasms - immunology; Lung Neoplasms - metabolism; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Lymphocytes T; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - metabolism; Lymphocytes, Tumor-Infiltrating - pathology; Macrophages; Macrophages - immunology; Macrophages - metabolism; Macrophages - pathology; Male; Medical prognosis; Medicine; Medicine and Health Sciences; Mesothelioma; Mesothelioma - immunology; Mesothelioma - metabolism; Mesothelioma - mortality; Mesothelioma - pathology; Mesothelioma, Malignant; Metastasis; Middle Aged; Neoplasm Staging; Patients; Phenotype; Pleural Neoplasms - immunology; Pleural Neoplasms - metabolism; Pleural Neoplasms - mortality; Pleural Neoplasms - pathology; Prognosis; Receptors, Cell Surface - metabolism; Surgery; Thoracic surgery; Tumor Microenvironment; Netherlands
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0106742

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. 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. 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. 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.