Tumor-infiltrating Leukocytes Suppress Local Inflammation Via Interleukin-1 Receptor Antagonist in a Syngeneic Prostate Cancer Model

Abstract

Background: Several lines of evidence have demonstrated the tumor-promoting function of inflammation. Since many chemokines are important in coordinating immune cells during inflammation, monitoring intratumoral chemokines provides a way to study the tumor microenvironment. Methods: To identify tumorigenic chemokines, we compared two syngeneic mouse prostate cancer cell lines by an antibody array and quantitative reverse-transcription polymerase chain reaction (RT-PCR). The tumor microenvironment was analyzed by monitoring gene expressions in mouse tumor tissues, primary cells, and tumor-infiltrating leukocytes (TILs). Result: We identified a group of pro-inflammatory chemokines associated with a tumorigenic transgenic adenocarcinoma mouse prostate (TRAMP)-C1 cell line. In the tumor microenvironment, the TILs secrete a natural anti-inflammatory factor, interleukin-1 receptor antagonist (IL1RN), which inhibits the functions of pro-inflammatory molecules and likely accounts for tumor type-specific anti-inflammation functions. Conclusion: Our results support that tumor cells recruit TILs by pro-inflammatory chemokines to establish an IL1RN-mediated anti-inflammatory environment in the syngeneic prostate cancer model.

Keywords

• tumor microenvironment
• tumor-infiltrating leukocytes
• interleukin-1 receptor antagonist