Abstract

Abstract Recently, expression of the regulatory T cell associated transcription factor, Foxp3, has been shown in a variety of tumors and tumor cell lines. The function of Foxp3 in tumor cells is currently unknown, but has implications for immune evasion and tumor progression. We have detected the presence of Foxp3 in several tumor cell lines, including 8 NSCLC lines, as well as in fresh tumor and normal adjacent tissue (NAT) samples by flow cytometry and western blot. To examine expression patterns in vivo, immunohistochemistry was performed on paraffin sections obtained from 25 NSCLC adenocarcinomas and 2 NAT. There was no evidence of Foxp3 expression in the normal lung tissues, however, all NSCLC samples included Foxp3+ tumor cells displaying either nuclear and/or cytoplasmic expression. Samples were graded 0-3, indicating no, weak, moderate or strong expression in each compartment. Strong nuclear expression was seen in 8 samples, moderate in 4 and weak in 8. Coefficient correlation analysis revealed a significant correlation (p=0.02) of nuclear expression strength with increasing histologic grade which was regardless of TNM staging. The analysis also suggests a relationship between nuclear Foxp3 expression in tumor cells and in infiltrating lymphocytes. As histologic grade has been reported as an independent prognostic factor for survival in NSCLC, we propose that Foxp3 may be an important element in promoting disease progression by inducing an immunosuppressive microenvironment.

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