No abstract

Vitiligo is a skin disorder characterized by depigmented macules secondary to melanocyte loss. An unusual facet is its relation to melanoma: Cytotoxic T lymphocytes directed to melanocyte antigens are found in both conditions and imply a breakdown of tolerance, yet the resulting immune reaction is the opposite. The mechanisms at the basis of these opposite effects are not known. Here, we performed a direct comparison of whole melanocyte-specific T cell populations in the two diseases. We demonstrate that neither precursor frequencies of Melan-A/MART-1-specific T lymphocytes nor their status of activation differ significantly. However, by using a tetramer-based T cell receptor down-regulation assay, we documented a higher affinity of vitiligo T cells. We calculated that the peptide concentration required for 50% of maximal receptor downregulation differed by 6.5-fold between the two diseases. Moreover, only vitiligo T cells were capable of efficient receptor down-regulation and IFN-c production in response to HLA-matched melanoma cells, suggesting that this difference in receptor affinity is physiologically relevant. The differences in receptor affinity and tumor reactivity were confirmed by analyzing Melan-A/MART-1-specific clones established from the two diseases. Our results suggest that the quality, and not the quantity, of the melanocytespecific cytotoxic responses differs between the two pathologies.

Introduction: Autologous fat transfer (AFT) is widely adopted for breast reconstruction, but its longterm oncologic safety is still not clearly established. The aim of the present study was to compare the 10-year loco-regional recurrence (LRR)-free and distant metastases (DM)-free survival probabilities in AFT vs. control patients, also evaluating the impact of AFT in different intrinsic molecular subtypes of breast cancer. Materials and Methods: 464 AFT patients were exactly matched with a cohort of 3,100 control patients treated between 2007 and 2017. A multivariate survival analysis was performed accounting for all variables related to LRR and DM, including adjuvant/neoadjuvant treatments. End-points were analyzed both overall and in each molecular subtype. Results: LRR occurred in 6.4% of AFT and in 5.0% of control patients (p=0.42), while DM were observed respectively in 7.7% and 5.4% of cases (p=0.20). AFT showed no effect on the 10-year LRR-free survival probability (adjusted HR 0.87, 95%CI 0.43-1.76, p=0.69) or the 10-year DM-free survival probability (adjusted HR 0.82, 95%CI 0.43-1.57, p=0.55). Luminal A patients treated by AFT showed a decreased LRR-free survival probability (HR 2.38, 95%CI 0.91-6.17, Log-Rank p=0.07), which was significantly lower than controls after 80 months (Log-Rank p=0.02). No differences in the 10-year event-free survival probability were found in Luminal B, HER2-positive or triple-negative patients. Conclusion: AFT does not increase breast cancer recurrence, with the possible exception of late LRRs for Luminal A patients, but further clinical and preclinical data are required to better clarify this data. The use of AFT should not be discouraged.

The original version of this article unfortunately contained mistakes. The names of all authors were inadvertently inverted and are now corrected in the author group of this article.