Forkhead Box P3-Positive Regulatory T Cells As Therapeutic Target for Breast Cancer

Abstract

TO THE EDITOR: In their article, Bates et al conclude that high numbers of forkhead box P3 (FOXP3)-positive regulatory T (Treg) cells represent an important marker for the identification of breast cancer patients at risk of late relapse. Similarly, patients with stage I non–small-cell lung cancer who have a higher proportion of tumor FOXP3-positive Treg cells relative to tumor-infiltrating T-cell lymphocytes have a significantly higher risk of recurrence. In pancreatic ductal carcinoma, a high prevalence of FOXP3-positive Treg cells seems to be a marker of poor prognosis. CD25 CD4 Treg cells, which specifically express the transcription factor FOXP3, are involved in the maintenance of immunological self-tolerance and suppressive control of aberrant immune responses. In contrast, they may impede the development of effective immunity to autologous tumor cells. As recently reported, only CCR7and L-selectin (CD62L) coexpressing cells within expanded CD4 T cells with high CD25 expression levels (CD25) maintain phenotypic and functional characteristics of Treg cells. These cells originate from CD45RA naive cells within the CD4 CD25 T-cell compartment. In particular, this subpopulation homogeneously expresses FOXP3, CD62L, CCR7, cytotoxic T lymphocyte– associated antigen-4, and maintains robust suppressive activity after expansion. In contrast, cell lines derived from CD45RA memory-type CD4 CD25 T cells show only moderate suppression and do not maintain FOXP3 expression. Although the CD4 CD25 Treg compartment in adult peripheral blood comprehends naive as well as memory cells, only the naive CD45RA subpopulation gives rise to homogeneous Treg cell lines, since memory-type Treg cells (CD45RA ) could downregulate FOXP3 expression and lose their suppressive activity. For this reason, we agree with Bates et al that FOXP3-positive Treg cells represent an important therapeutic target for breast cancer.