Abstract
BackgroundRegulatory T cells (Treg) expressing the transcription factor forkhead-box protein P3 (Foxp3) have been identified to counteract anti-tumor immune responses during tumor progression. Besides, Foxp3 presentation by cancer cells itself may also allow them to evade from effector T-cell responses, resulting in a survival benefit of the tumor. For colorectal cancer (CRC) the clinical relevance of Foxp3 has not been evaluated in detail. Therefore the aim of this study was to study its impact in colorectal cancer (CRC).Methods and FindingsGene and protein analysis of tumor tissues from patients with CRC was performed to quantify the expression of Foxp3 in tumor infiltrating Treg and colon cancer cells. The results were correlated with clinicopathological parameters and patients overall survival. Serial morphological analysis demonstrated Foxp3 to be expressed in cancer cells. High Foxp3 expression of the cancer cells was associated with poor prognosis compared to patients with low Foxp3 expression. In contrast, low and high Foxp3 level in tumor infiltrating Treg cells demonstrated no significant differences in overall patient survival.ConclusionsOur findings strongly suggest that Foxp3 expression mediated by cancer cells rather than by Treg cells contribute to disease progression.
Highlights
The identification of CD4+CD25+ T regulatory cells (Treg) has been shown to play a crucial role in maintaining immunologic tolerance
Our findings strongly suggest that forkhead-box protein P3 (Foxp3) expression mediated by cancer cells rather than by Treg cells contribute to disease progression
To analyze whether CD4, CD25, Foxp3, IL-10, and TGFb expression in colorectal cancer (CRC) may be associated with clinical tumor progression we investigated tumors of limited disease (UICC I/II) and advanced disease (UICC III/IV)
Summary
The identification of CD4+CD25+ T regulatory cells (Treg) has been shown to play a crucial role in maintaining immunologic tolerance. The transcription factor forkhead box protein P3 (Foxp3) has been identified as a key player in Treg function and is an obligate marker of CD4+CD25+ Treg [1]. A high density of tumor infiltrating Foxp3+ Treg in tumor specimen has been associated with poor outcome in various solid tumors, including ovarian [4], pancreatic [5], and hepatocellular carcinoma [6]. These findings suggest a crucial role for Treg in different tumor entities. Regulatory T cells (Treg) expressing the transcription factor forkhead-box protein P3 (Foxp3) have been identified to counteract anti-tumor immune responses during tumor progression. The aim of this study was to study its impact in colorectal cancer (CRC)
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