Prognostic value of tumor-infiltrating Foxp3+ T-cell subpopulations in metastatic melanoma

Abstract

Regulatory T cells have already been associated with poor prognosis in various types of cancer. It was previously reported, in ovarian carcinoma, that quantification of Foxp3 identified a subgroup of patients characterized by a significantly worse prognosis in terms of overall survival (OS) and progression‐free survival (PFS), suggesting that high expression levels of Foxp3 might represent a surrogate marker for an immunosuppressive microenvironment contributing to tumor immune escape. The main objective of the present study was to precise the prognostic value of Foxp3 regarding PFS and OS in stage III (AJCC) melanoma patients. Total RNA was isolated from 102 metastatic melanoma lymph nodes and from eight tumor‐free lymph nodes. Real‐time PCR for Foxp3 was performed and correlated with patients’ outcome. Quantification of Foxp3 identified a patient subgroup (>90th percentile), which is characterized by a significantly worse prognosis in terms of PFS (P = 0.000271) but not in terms of OS (P = 0.11). In conclusion, quantification of Foxp3 expression using qPCR appears as an independent prognostic factor for PFS in stage III melanoma patients (AJCC). High Foxp3 expression might thus enable the identification of patients most at risk of relapse.

Infiltration of effector regulatory T cells predicts poor prognosis of diffuse large B-cell lymphoma, not otherwise specified

“…[20][21][22][23][24][25] In contrast, a high infiltration of Tregs has been reportedly associated with an improved OS in colorectal cancer. 26 Although FOXP3 expression has been used as a specific marker of Tregs, 27 FOXP3-positive cells were revealed to include cells heterogeneous in both phenotype and function.…”

FoxP3 and indoleamine 2,3-dioxygenase immunoreactivity in sentinel nodes from melanoma patients

“…Intratumoral Treg prevalence has been shown to be an independent negative prognostic marker for uveal melanoma [30]. Knol et al [24] showed that Tregs decrease progression free survival in allsite metastatic melanoma. The prognostic significance of IDO immunoreactivity in addition to metastasis has also been shown in SLNs of 160 patients in all-site melanoma by Speeckaert et al [31].…”

“…Staining for CD3 and CD4 was also initially performed to confirm that the FoxP3+ cells represented T cells, rather than another FoxP3+ cell type. FoxP3 positivity alone has previously been used as the most specific marker of Tregs [15,[24][25][26].…”

Is it possible to overcome antiapoptotic API2/MALT1 events in tumor B-cells by influencing Tregs in MALT lymphoma?

“…The presence of a high number of Tregs in a variety of malignancies has been correlated with poor prognosis (such as melanoma, ovarian carcinoma and Ewing sarcoma) [17][18][19] or favorable prognosis (colorectal adenocarcinoma) [20]. Furthermore, there seems to be a stage-related increase of Treg density [21].…”