Malignant Peritoneal Mesothelioma: Characterization of the Inflammatory Response in the Tumor Microenvironment

Our plain-English summary of Malignant Peritoneal Mesothelioma: Characterization of the Inflammatory Response in the Tumor Microenvironment, by S. Judge, P. Thomas, V. Govindarajan, et al (Annals of Surgical Oncology, 2016).

The study

• Authors: S. Judge, P. Thomas, V. Govindarajan, P. Sharma, B. Loggie
• Journal: Annals of Surgical Oncology
• Published: 2016;23(5):1496-500
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Malignant peritoneal mesothelioma (MPM) is a rare cancer arising from mesothelial cells lining the peritoneal surface. Little is known about the tumor microenvironment in regulating MPM oncogenesis. The current study defined the chemokine/cytokine expression profile and inflammatory responses within the MPM microenvironment.

Methods: Levels of 10 cytokines (Fractalkine, IFNγ, IL-6, IL-8, IP-10, MCP-1, MIP-1α, MIP-1β, TNFα, VEGF) in matched ascites and sera from 15 MPM patients were measured using Milliplex immunoassays. Sera from six normal control sera were included. Statistical analyses included the Wilcoxon signed-rank test, the Mann-Whitney U test, bivariate analysis, and the R (2) coefficient of correlation.

Results: The median levels of IL-6 (3190 vs 3.18 ng/ml; p < 0.001), IL-8 (118 vs 4.93 ng/ml; p < 0.001), IP-10 (3923 vs 384 ng/ml; p < 0.001), and MCP-1 (2886 vs 544 ng/ml; p = 0.005) were significantly higher in the MPM ascites than in the matched MPM serum. In the MPM serum samples, the levels of IL-8 (4.93 vs 1.52 ng/ml; p = 0.002), MIP-1β (53.8 vs 22.3; p = 0.016), TNFα (9.97 vs 4.5 ng/ml; p = 0.013), and VEGF (277 vs 105.4 ng/ml; p = 0.036) were significantly higher than in the control sera.

Conclusion: The chemokines/cytokines in the MPM tumor microenvironment are distinct from those associated with inflammatory responses to infection or injury (e.g., IL-1, IL-2, TNFα, IFNγ). These local changes reflect active reciprocal communication between tumor and associated stroma, which the authors predict is integral to MPM oncogenesis. Future studies will test this hypothesis and identify potential serum biomarkers for MPM.

In plain English

This laboratory study, from Creighton University in Omaha, Nebraska, measured 10 inflammation-related signaling proteins (cytokines and chemokines) in people with malignant peritoneal mesothelioma, a cancer of the abdominal lining. Fluid from the abdomen (ascites) and blood were taken from 15 patients at the time of surgery. Blood was also taken from six healthy adults. The article does not report the patients' asbestos exposure. Four proteins had significantly higher median levels in the patients' ascites than in their own blood: IL-6 (3190 vs 3.18 pg/ml), IL-8 (118 vs 4.93 pg/ml), IP-10 (3923 vs 384 pg/ml) and MCP-1 (2886 vs 544 pg/ml). In blood, four proteins were significantly higher in patients than in healthy adults: IL-8 (4.93 vs 1.52 pg/ml), MIP-1 beta (53.8 vs 22.32 pg/ml), TNF-alpha (9.97 vs 4.5 pg/ml) and VEGF (277 vs 105.4 pg/ml). IL-8 was the only protein significantly raised in both comparisons. The authors concluded that IL-8 may be a major mediator in the tumor's surroundings. They proposed that this protein pattern might be used to judge prognosis and response to treatment. They named the small number of patients as a limitation.

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: Laboratory study comparing levels of 10 cytokines/chemokines in matched ascites and blood serum from patients, and in serum from healthy controls
• Who was studied: 15 patients with malignant peritoneal mesothelioma (ascites and blood taken at surgery) and six healthy adults (blood only), at Creighton University, Omaha, Nebraska; study dates not given
• Exposure: Not reported. The article does not describe asbestos or any other exposure of the patients. It measured 10 cytokines/chemokines: Fractalkine, interferon gamma, IL-6, IL-8, IP-10, MCP-1, MIP-1 alpha, MIP-1 beta, TNF-alpha and VEGF.
• Main results:
  • Ascites compared with matched serum in the 15 patients: median IL-6 was 3190 vs 3.18 pg/ml and IL-8 was 118 vs 4.93 pg/ml (both p less than 0.001).
  • Ascites compared with matched serum in the 15 patients: median IP-10 was 3923 vs 384 pg/ml (p less than 0.001) and MCP-1 was 2886 vs 544 pg/ml (p = 0.005).
  • Four other proteins (Fractalkine, interferon gamma, MIP-1 beta and VEGF) were higher in patients' serum than in their ascites, but the differences were not statistically significant.
  • Patient serum (n = 15) compared with control serum (n = 6): median IL-8 was 4.93 vs 1.52 pg/ml (p = 0.002).
  • Patient serum compared with control serum: MIP-1 beta was 53.8 vs 22.32 pg/ml (p = 0.016), TNF-alpha 9.97 vs 4.5 pg/ml (p = 0.013) and VEGF 277 vs 105.4 pg/ml (p = 0.036).
  • No protein was higher in the healthy controls than in the patients. The six proteins that did not differ significantly were all higher in the patients.
  • IL-8 was the only protein significantly raised in both comparisons: patient ascites vs patient serum, and patient serum vs control serum.
• The authors' conclusion: The authors concluded that IL-8 may be a major mediator in the tumor microenvironment of malignant peritoneal mesothelioma. They proposed that this disease has a specific cytokine/chemokine pattern, different from other cancers, that might be used to determine prognosis and response to therapy.
• Limitations the authors state:
  • The study involved a small number of patients, which the authors say is inherent to research on rare diseases.
  • The study did not determine whether the cytokines came from the tumor or from the surrounding tissue (stroma).

Topics

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

Medical terms in this study, explained in our Lexicon: Peritoneal Mesothelioma, Tumor Microenvironment, Mesothelial Cells, Oncogenesis, Cytokine, Ascites, Biomarker.

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