Quantification of Regulatory T Cells Enables the Identification of High-Risk Breast Cancer Patients and Those at Risk of Late Relapse

Abstract

These findings indicate that quantification of FOXP3-positive TR in breast tumors is valuable for assessing disease prognosis and progression, and that TR are an important therapeutic target for breast cancer. FOXP3-positive TR represent a novel marker for identifying late-relapse patients who may benefit from aromatase therapy after standard tamoxifen treatment.

Tumor-Infiltrating Regulatory T Cells: Phenotype, Role, Mechanism of Expansion In Situ and Clinical Significance

“…Tumor infiltration by Tregs, near-to-invariably detected by the immunohistochemical detection of FOXP3 + lymphocytes, has been associated with poor prognosis in cohorts of patients affected by multiple distinct neoplasms, including Hodgkin lymphoma, melanoma as well as breast, gastric and ovarian carcinoma [29, [91][92][93][94]. In line with these results, it has been shown that clinical response to chemotherapy is often associated with a reduction in TITregs and the recruitment of intratumoral CD8 + T cells [95].…”

Human FOXP3 and cancer

“…FOXP3 þ cells were sometimes localized in the vicinity of tumor cells, but rather predominant in the peripheral lymphoid-enriched areas (Curiel et al, 2004;Mizukami et al, 2008;Gobert et al, 2009). The density of FOXP3 þ cells was reported to be significantly higher in malignant than in normal tissue (Bates et al, 2006;Hiraoka et al, 2006;Miller et al, 2006;Mizukami et al, 2008). However, it should be noted that all tumor-infiltrating FOXP3 þ cells were not inevitably Tregs because TCR activation of conventional T cell may be sufficient for inducing FOXP3 transient expression without suppressive properties, as discussed above.…”

Regulatory T cells in cancer immunotherapy

“…In humans, tumors in the head and neck [41], breast [42], lung [43], liver [44], gastrointestinal tract [45,46], pancreas [47], and ovary [48,49] have been shown to harbor a large number of tumor-infiltrating Treg cells [50]. Importantly, decreased ratios of tumor-infiltrating CD8 + T cells to FOXP3 + Treg cells were shown to correlate with poor prognosis, especially in patients with breast [51], gastric [46], and ovarian cancer [48,49]. Furthermore, a recent meta-analysis of previously published data indicated that in majority of solid tumors in the cervix, kidney, breast, and melanomas, high frequency of tumor-infiltrating FOXP3 + cells was significantly negatively correlated with patients' survival [52].…”