High frequency of tumor-infiltrating FOXP3+ regulatory T cells predicts improved survival in mismatch repair-proficient colorectal cancer patients
✍ Scribed by Daniel M. Frey; Raoul A. Droeser; Carsten T. Viehl; Inti Zlobec; Alessandro Lugli; Urs Zingg; Daniel Oertli; Christoph Kettelhack; Luigi Terracciano; Luigi Tornillo
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- French
- Weight
- 331 KB
- Volume
- 126
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Regulatory T cells (T reg ) inhibit the generation of host-versus-tumor immunity via suppression of tumor-specific effector T-cell responses and development of immune tolerance to neoplastic cells. The transcription factor forkhead box P3 (FOXP3) is an intracellular key molecule for T reg development and function and is considered to represent the most specific T reg cell marker. The aim of this study was to analyze the frequency and prognostic impact of tumor-infiltrating FOXP3 1 T reg in colorectal cancer (CRC) stratified by mismatch-repair (MMR) status. Using the tissue microarray technique, 1,420 tumor samples were immunohistochemically stained for FOXP3 and stratified into 1,197 MMR-proficient and 223 MMR-deficient CRCs. Additionally, the 1,197 MMR-proficient CRCs were randomized into 2 subgroups (Test Groups 1 and 2; n 5 613 and 584, respectively). In both MMR-proficient CRC subgroups high frequency tumor-infiltrating FOXP3 1 T reg was associated with early T stage (p 5 0.001 and <0.001), tumor location (p 5 0.01 and 0.045) and increased 5-year survival rate (p 5 0.004 and <0.001), whereas in MMR-deficient CRCs an association between FOXP3 1 T reg and absence of lymph node involvement (p 5 0.023), absence of vascular invasion (p 5 0.023) and improved 5-year survival rate (p 5 0.029) could be detected. In a multivariable analysis including age, gender, T stage, N stage, tumor grade, vascular invasion, and tumor border configuration, a high FOXP3 1 T reg frequency was an independent prognostic factor in both MMR-proficient CRC subsets (p 5 0.019 and p 5 0.007), but not in the MMR-deficient CRCs (p 5 0.13). Therefore, high frequency of tumor-infiltrating FOXP3 1 T reg is associated with early T stage and independently predicts improved disease-specific survival in MMR-proficient CRC patients.