Immunohistochemical distribution of FOXP3+ regulatory T cells in colorectal cancer patients

Background: Recent studies have focused on less invasive methods for diagnosing and predicting survival outcomes for colorectal cancer (CRC) patients. Objective: We studied the role of the transcription factor forkhead box P3 (FOXP3) in the tumorigenesis of CRC and investigated its prognostic value in survival outcome estimates. Methods: FOXP3+ regulatory T (Treg) cell levels in CRC and adjacent tissues were measured by immunohistochemistry (IHC) and compared statistically. A literature search was conducted on FOXP3+ Treg cell density and survival rates, including overall survival, disease-free survival, and cancer-specific survival. Meta-analyses were then performed to determine the prognostic value of FOXP3+ Treg cell levels in CRC patients. Results: FOXP3+ Treg cells were increased in CRC tissues over adjacent controls according to the IHC results (t = 14.321; P < 0.001) and cell densities in cases with metastases were higher than those without metastasis (P < 0.05). Cases with serosal infiltration showed higher FOXP3+ Treg cell densities compared to cases without infiltration (P < 0.05) and cell densities in cases differentiated to a lower degree than in cases showing a medium to high degree of differentiation (P < 0.05). Moreover, meta-analysis found a high FOXP3+ Treg cells density in CRC tissues (standardized mean differences = 0.30 [95% CI: 0.03-0.57]), which was correlated with better overall patient survival outcome (hazard ratio = 0.749 [95% CI: 0.648-0.867]). Conclusions: Increased FOXP3+ Treg cells may be an effective marker for tumorigenesis and clinical prognostic evaluation for CRC patients.