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

Our plain-English summary of Intratumoral macrophage phenotype and CD8+ T lymphocytes as potential tools to predict local tumor outgrowth at the intervention site in malignant pleural mesothelioma, by R. Cornelissen, L.A. Lievense, J.L. Robertus, et al (Lung Cancer, 2015).

The study

• Authors: R. Cornelissen, L.A. Lievense, J.L. Robertus, R.W. Hendriks, H.C. Hoogsteden, J.P. Hegmans, J.G. Aerts
• Journal: Lung Cancer
• Published: 2015;88(3):332-7
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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.

Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

In plain English

This study from Rotterdam, the Netherlands, concerned malignant pleural mesothelioma patients whose tumor grew out along the track of an earlier procedure, such as a biopsy needle, chest tube or thoracoscopy. This is called local tumor outgrowth, or LTO. The authors looked back at stored diagnostic biopsies from 10 patients who developed LTO and from 10 patients who did not, matched for age, tumor histology, diagnostic procedures, treatment and survival. They counted immune cells: all macrophages (CD68), the M2 type of macrophage (CD163) and CD8+ T cells. Total macrophage and M2 counts were similar in the two groups. The share of M2 macrophages among all macrophages averaged 0.9 in the LTO group and 0.63 in the non-LTO group (p less than 0.001). CD8+ T cells averaged 30 per 0.025 cm2 in the LTO group and 140 in the non-LTO group (p less than 0.01). The study did not examine asbestos exposure. The authors concluded that these measures could help predict which patients are prone to LTO. They called the method preliminary because only a small number of patients were studied.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective comparison of stored diagnostic biopsies from patients who developed local tumor outgrowth and matched patients who did not, using immunohistochemistry
• Who was studied: 20 malignant pleural mesothelioma patients at the Erasmus MC Cancer Institute, Rotterdam, the Netherlands. 10 were diagnosed between 2008 and 2012 and developed LTO. The other 10 did not develop LTO and were matched for age, tumor histology, diagnostic procedures, treatment and survival. None received prophylactic irradiation of the intervention track.
• Exposure: Asbestos exposure was not studied. The factors compared were immune cells in diagnostic biopsies: all macrophages (CD68), M2 macrophages (CD163) and CD8+ T cells, measured after diagnostic or therapeutic procedures.
• Main results:
  • Counts of all macrophages (CD68) and of M2 macrophages (CD163) were comparable between the LTO group and the non-LTO group. CD68 averaged 185.1 versus 219.8 per 0.025 cm2 (p = 0.4). CD163 averaged 170.5 versus 135 per 0.025 cm2 (p = 0.9).
  • The average ratio of M2 macrophages to all macrophages was 0.9 (SD 0.09) in the LTO group and 0.63 (SD 0.09) in the non-LTO group (p less than 0.001).
  • CD8+ T cell counts were higher in patients who did not develop LTO: 140 per 0.025 cm2 (range 23 to 314), compared with 30 per 0.025 cm2 (range 2 to 60) in patients who developed LTO (p less than 0.01).
  • The correlation between CD8+ T cell count and the M2 to total macrophage ratio was not statistically significant (Spearman's rho of minus 0.40, p = 0.08). All patients who developed LTO clustered in the high-ratio, low-CD8 area.
• The authors' conclusion: The authors concluded that the macrophage phenotype ratio and CD8+ T cell count in diagnostic biopsies offer an opportunity to predict which malignant pleural mesothelioma patients are prone to LTO after a local intervention. They described this as a preliminary method.
• Limitations the authors state:
  • The hypothesis could only be tested on a limited number of patients, so the authors regard this as a preliminary method.
  • These immune cells have been linked to survival in earlier studies. Although patients were matched for survival, future studies are needed to separate effects on survival from effects on LTO.
  • Only single-staining immunohistochemistry was used. Additional markers would be useful to identify M2 macrophages in more detail.
  • Larger studies are needed to validate the approach and to set proper cut-off values.
  • Other immune cell types in the tumor were not analyzed, and staining is not yet available for all of them.
  • Only small diagnostic biopsy specimens were available, so the type, location, density and function of immune cells could not be properly studied.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Macrophage, Pleural Mesothelioma, Biomarker, Mesothelioma, Immunohistochemistry.

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• Depletion of Tumor-Associated Macrophages with a CSF-1R Kinase Inhibitor Enhances Antitumor Immunity and Survival Induced by DC Immunotherapy — F. Dammeijer, L.A. Lievense, et al. (2017)
• Deliberately provoking local inflammation drives tumors to become their own protective vaccine site — C. Jackaman, A.M. Lew, et al. (2008)
• Tumor-associated macrophages in thoracic malignancies — L.A. Lievense, K. Bezemer, et al. (2013)
• Tumor-associated macrophage-derived inflammatory cytokine enhances malignant potential of malignant pleural mesothelioma — D. Horio, T. Minami, et al. (2020)
• NOX4 modulates macrophage phenotype and mitochondrial biogenesis in asbestosis — C. He, J.L. Larson-Casey, et al. (2019)

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