The avidity of tumor-specific T cells amplified by a plasmacytoid dendritic cell-based assay can predict the clinical evolution of melanoma patients.

ABSTRACT

The advent of immune checkpoint blockers and targeted therapies has changed the outcome of melanoma. However, many patients experience relapses, emphasizing the need for predictive and prognostic biomarkers. We developed a strategy based on plasmacytoid dendritic cells (pDCs) loaded with melanoma tumor antigens that allows eliciting highly efficient antitumor T-cell responses. We used it to investigate antitumor T-cell functionality in peripheral blood mononuclear cells and tumor-infiltrating lymphocytes from melanoma patients. The pDCs elicited tumor-specific T cells in different proportions and displaying diverse functional features, dependent upon the stage of the disease, but independent of the histological parameters at diagnosis. Strikingly, the avidity of the MelA-specific T cells triggered by the pDCs was found to predict patient relapse time and overall survival. Our findings highlighted unexplored aspects of antitumor T-cell responsiveness in melanoma, and revealed for the first time the structural avidity of tumor-specific T cells as a crucial feature for predicting clinical evolution.