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

Summary

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.

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