FOXP3+ regulatory T cells in cutaneous T-cell lymphomas: association with disease stage and survival

Abstract

FOXP3 is a unique marker for CD4 þ CD25 þ regulatory T cells (Tregs). In solid tumours, high numbers of Tregs are associated with a poor prognosis. Knowledge about the implications of Tregs for the behaviour of haematological malignancies is limited. In this study, skin biopsies from 86 patients with mycosis fungoides (MF) and cutaneous T-cell lymphoma (CTCL) unspecified were analysed for the expression of FOXP3 on tumour cells and tumour-infiltrating Tregs. Labelling of above 10% of the neoplastic cells was seen in one case classified as an aggressive epidermotropic CD8 þ cytotoxic CTCL. In the remaining 85 cases, the atypical neoplastic infiltrate was either FOXP3 negative (n ¼ 80) or contained only very occasional weakly positive cells (n ¼ 5). By contrast, all biopsies showed varying numbers of strongly FOXP3 þ tumour-infiltrating Tregs. MF with early or infiltrated plaques had significantly higher numbers of FOXP3 þ Tregs than CTCL unspecified or advanced MF with tumours or transformation to large cell lymphoma. An analysis of all patients demonstrated that increasing numbers of FOXP3 þ Tregs were associated with improved survival in both MF and CTCL unspecified. In conclusion, our data indicate that the presence of FOXP3 þ Tregs in CTCL is associated with disease stage and patient survival.

FOXP3+ Cell Density in Primary Tumor Has No Prognostic Impact in Patients with Cutaneous Malignant Melanoma

“…Since the amount of FOXP3 + cells did not show association with any of the studied parameters: patient age or gender, tumor thickness, location, histological type, ulceration and, most importantly, the outcome of the disease, as mentioned above, FOXP3 + cell infiltration in the primary tumor does not seem to have a significant impact on the course of the disease in cutaneous melanoma. Previous studies aiming at the clinical relevance of tumor-infiltrating Tregs have given rise to contradictory results, showing correlation with poor outcome in some cancer types [5][6][7][8][9] but no association or even correlation with improved survival in others [10][11][12][13][14][15][16][17]21]. It could be suggested that each tumor type behaves differently in this context [4], depending perhaps on other players on the scene of antitumor immune reactions and their complex functional interrelationships with Tregs as well as with tumor cells.…”

“…Reports on the prognostic role of tumor-infiltrating Tregs are inconclusive; while in some cancer types their increased level has been correlated with poor outcome, as in the case of ovarian, breast, pancreatic and hepatocellular carcinomas [5][6][7][8][9], in others including prostate and renal cancers no significant associations were found [10,11], and in the case of head and neck carcinomas, colorectal cancer, as well as in several lymphoma types a marked infiltration by Tregs showed correlation with improved survival [12][13][14][15][16][17].…”

STAT5-mediated expression of oncogenic miR-155 in cutaneous T-cell lymphoma

“…Samples were drawn from the archives of the Departments of Pathology at Rigshospitalet (Copenhagen University Hospital) and Bispebjerg Hospital and have been described in detail elsewhere. 48 For immunohistochemistry, 47 cases were selected for analysis. Fourteen patients had MF with patches, and 21 had plaques.…”

Cutaneous T‐cell lymphoma: 2011 update on diagnosis, risk‐stratification, and management

“…Therefore, FoxP3 expression alone, particularly at low-intermediate levels, as observed in activated T cells and in some patients with CTCL, is insufficient evidence to support the claim that clonal T cells in MF or SS are Treg-derived, particularly considering the observation that conventional T cells may acquire a similar Treg-phenotype when cultured under similar conditions [24,25]. Subsequent histologic analyses of FoxP3 expression by immunohistochemical staining demonstrate that malignant T cells in CTCL lesions do not express FoxP3 to any significant degree [26,27]. As FoxP3 expression is not entirely specific for Treg cells, the definition of ''Treg cells'' has been, at least in part, a functional one.…”