Abstract
Background Chemotherapy and vaccination with tumor-loaded dendritic cells (DCs) show poor impact on overall survival (OS) in metastatic melanoma. Ipilimumab (IPI) improves OS throughout the blockade of CTLA4-mediated inhibitory signals in T-cells and restores the efficiency of the antigenic cross-priming by mature (m) DCs. However, variation of immune cells to evaluate the response to IPI does not reflect the T-cell activation and is a modest predictor of clinical response. Recent studies in human and experimental melanoma demonstrated that mDCs release endomysial microvescicles namely dexosomes (Dex) showing a functional anti-melanoma activity as well as an antigenic profile resembling that of circulating mDCs including CD40, CD80 and CD86 co-stimulatory molecules. This research is aimed to identify an early biomarker of T-cell activation for predicting the clinical response in IPItreated melanoma patients.
Highlights
Chemotherapy and vaccination with tumor-loaded dendritic cells (DCs) show poor impact on overall survival (OS) in metastatic melanoma1,2
Recent studies in human and experimental melanoma demonstrated that mDCs release endomysial microvescicles namely dexosomes (Dex) showing a functional anti-melanoma activity as well as an antigenic profile resembling that of circulating mDCs including CD40, CD80 and CD86 co-stimulatory molecules
Dex were first identified by size and CD40, CD80 and CD86 expression was evaluated by flow-cytometry using relative MoAbs
Summary
Chemotherapy and vaccination with tumor-loaded dendritic cells (DCs) show poor impact on overall survival (OS) in metastatic melanoma. Ipilimumab (IPI) improves OS throughout the blockade of CTLA4-mediated inhibitory signals in T-cells and restores the efficiency of the antigenic cross-priming by mature (m) DCs3. Variation of immune cells to evaluate the response to IPI does not reflect the T-cell activation and is a modest predictor of clinical response. Recent studies in human and experimental melanoma demonstrated that mDCs release endomysial microvescicles namely dexosomes (Dex) showing a functional anti-melanoma activity as well as an antigenic profile resembling that of circulating mDCs including CD40, CD80 and CD86 co-stimulatory molecules. This research is aimed to identify an early biomarker of T-cell activation for predicting the clinical response in IPItreated melanoma patients
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