Kidney Week

Abstract: SA-PO463

Autosomal Dominant Polycystic Kidney Disease Shows a Tumor-Like Microenvironment

Session Information

• Cystic Kidney Diseases: Basic/Translational
  November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1001 Genetic Diseases of the Kidneys: Cystic

Authors

• Nigro, Elisa Agnese, San Raffaele Scientific Institute, Milan, Italy

Elisa Agnese Nigro,

• Steidl, Maria Elena, San Raffaele Scientific Institute, Milan, Italy

Maria Elena Steidl,

• Chiaravalli, Marco, San Raffaele Scientific Institute, Milan, Italy

Marco Chiaravalli,

• Boletta, Alessandra, San Raffaele Scientific Institute, Milan, Italy

Alessandra Boletta,

Background

Polycystic kidney disease (PKD) is an inherited genetic disorder characterized by progressive growth of cysts in the kidneys. Despite not being a cancer, PKD shares many features with tumors. For instance, recent studies suggest a role of immune cells in PKD progression. Tumor modifies infiltrating cells functions to create the microenvironment favorable to tumor progression. Principal components of the Tumor Microenvironment (TME) are immune-inflammatory cells, Cancer-Associated Fibroblasts (CAFs), blood vessels and ECM. We investigated whether a similar environment might be present in PKD murine models.

Methods

We have characterized the renal tissue microenvironment of a Pkd1^flox/-:TmCre inducible and the Pkd1^flox/-:KspCre ADPKD mouse models. We have analyzed the presence of infiltrating immune cells and CAFs, and the state of the ECM through histological analysis and quantitative Real Time-PCR. In addition fluorometric analysis following dissociation of cells from total kidneys was used to analyze interstitial inflammation. For the pan macrophages quantification, we have performed an in situ quantification employing an F4/80 detection algorithm.

Results

We have detected a statistically significant increased level of CD45⁺ leukocytes in the ADPKD kidneys compared to the controls. In contrast, B and T lymphocytes could not be detected in late PKD models. Macrophages, activated myofibroblasts (potentially corresponding to CAFs), and extensive fibrosis in the kidneys of the ADPKD affected mice could be detected. In particular, while M1-macrophages (expressing Nos2) did not significantly change between the PKD kidneys and the controls, M2-macrophages (expressing Arg1) were found significantly increased in the kidneys of PKD mice compared to controls.

Conclusion

Our analysis on the kidneys of the ADPKD mouse models reveals the presence of a tumor-like microenvironment (T-LME), which could promote disease progression. The analysis of the crosstalk among the different components of the microenvironment might provide important insights into disease progression in PKD.