Regulatory T-cells induce an immune escape in a murine model of primary intraocular B-cell lymphoma

Abstract

Purpose The role of regulatory T cells (Tregs) in the immune evasion of tumors is usually prominent. The aim of this study was to assess the presence and role of Tregs in a murine model of primary intraocular B-cell lymphoma (PIOL). Methods We used a syngeneic model of PIOL in immunocompetent BALB/c mice. Immunohistochemistry and flow cytometric analysis have been performed to study the tumor growth and the immune infiltrate. Depletion of Tregs was achieved using intraperitoneal injection of anti-CD25 mAb (PC61). Splenectomy was performed to study the role of induced Tregs. Results Tregs were recruited in PIOL eyes (16.2%) compared to control eyes (1.2%, p<0.001). The number of infiltrating Tregs was correlated with tumor burden (r2=0.76), and inversely correlated with CD4+ T-cells (r2=-0.79). Recruitment of Tregs was also observed in the spleen of mice bearing tumor (2.9%) compared to controls (2.1%, p<0.001), but not in the draining lymph nodes. Depletion of Tregs resulted in a significant decrease of tumor burden (53.8% in control mice compared to 37.7% in PC61 mice, p=0.03), and an increase of the immune infiltrate. Splenectomy experiments comfirmed the role of iTregs in tumor escape. Eventhough the number of tumor cells decreased, tumor growth could not be abrogated. Conclusion We demonstrated that Tregs are recruited in the tumor microenvironment. Tregs limit the recruitement of CD4+ T-cells in the eyes and are thought to inhibit their effector functions. The mechanisms by which Tregs are generated could be similar to ACAID, yet in the posterior chamber. Several escape mechanisms are responsible for tolerance toward the tumor in the eye.