gms | German Medical Science

Introduction: Identification of CD4+CD25+ regulatory T cells (Treg) has been shown to play a role in maintaining immunologic tolerance. The transcription factor forkhead box P3 (Foxp3) has been identified as a key player in Treg function and is a definitive marker of CD4+CD25+ Treg. The purpose of this study was to evaluate the prognostic value of Foxp3 during colorectal cancer (CRC) progression as a potential escape mechanism in CRC.

Materials and methods: Patients with CRC (n=65) undergoing curative resection were included in the study. The staining of CD4, CD25, Foxp3, TGF-β, and IL-10 was performed in CRC specimens in early and late stage tumors (UICC I/II vs UICC III/IV) and 12 normal colon specimens. Gene expression of all markers was performed using Real Time PCR. Kaplan-Meier and univariate/multivariate analysis were used for statistical analysis.

Results: First we analyzed whether CD4, CD25, Foxp3, TGF-β, and IL-10 expression within the tumor was clinically associated with tumor progression. qRT-PCR and immunohistochemical analysis showed significantly increased gene/protein expression of CD4 and CD25 in early compared to advanced disease and normal tissue. In addition, Foxp3 (60/65) and immunosuppressive cytokines IL-10 and TGF-β were significantly increased in early and advanced disease compared to normal tissue. Increased CD4+, CD25+, Foxp3+ (61/65), IL-10+, and TGF-β+ expression was observed associated with tumor infiltrating lymphocytes (TILs) in early compared to advanced disease and normal tissue. Furthermore, among patients with CRC, those with high Foxp3 expressing tumor tissues had a poorer prognosis than those with low Foxp3 tumor tissues. Moreover, there was no significant difference in the overall survival by comparing patients with low and high Foxp3+ expressing TILs.

Conclusion: We conclude that Foxp3+ tumor tissues may be rather related to immunosuppression and tumor progression than Foxp3 expression by TILs. Therefore vaccination against Foxp3+ tumor tissues may be an effective strategy of treatment in patients with CRC.