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

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.

Propionibacterium acnes activates the IGF-1/IGF-1R system in the epidermis and induces keratinocyte proliferation.

Propionibacterium acnes has a major role in the development of acne lesions. IGF-1 stimulates the proliferation of keratinocytes via an activation of the IGF-1 receptor (IGF-1R). Zinc has been proven to work efficiently against inflammatory acne and to modulate the IGF-1 system. Our objectives were to study the modulation of IGF-1 and IGF-1R expression by P. acnes extracts and to determine their modulation by zinc gluconate. In vivo, we analyzed biopsies of acne lesions and healthy skin, and in vitro we used skin explants incubated with two P. acnes extracts--membrane fraction (MF) and cytosolic proteins--with or without zinc. IGF-1 and IGF-1R expression was evaluated using immunohistochemistry, and the IGF-1 production in supernatants was measured by ELISA. Then, IGF-1 and IGF-1R mRNA levels were analyzed using quantitative PCR on normal human epidermal keratinocytes (NHEKs). IGF-1 and IGF-1R were overexpressed in acne lesions. MF increased IGF-1 and IGF-1R expression in the epidermis of explants and was associated with an overexpression of both Ki-67 and filaggrin. Zinc had the effect of downregulating IGF-1 and IGF-1R levels. These observations were confirmed at the mRNA level for IGF-1R in NHEKs. These results demonstrate that P. acnes can induce the formation of comedones by stimulating the IGF/IGF-1R system. Moreover, zinc downregulates this pathway.