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

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.