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

Recent studies have focused on less invasive methods for diagnosing and predicting survival outcomes for colorectal cancer (CRC) patients. 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. 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. 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]). Increased FOXP3+ Treg cells may be an effective marker for tumorigenesis and clinical prognostic evaluation for CRC patients.