Beschreibung:
<jats:title>Abstract</jats:title>
<jats:p>Identification and isolation of mutation-specific T-cells is a major obstacle to the development of effective cancer immunotherapies. The tumor is a natural sink for neo-antigen specific cells, but these are far less frequent in peripheral blood, a more accessible and abundant source of T cells. Previous studies have revealed that PD-1 expression in the tumor microenvironment can identify the patient-specific repertoire of tumor and mutation-specific cells infiltrating human tumors. Here, we evaluated the potential utility of PD-1 expression on circulating lymphocytes to identify and enrich for mutation-specific cells. Selection of CD8+PD-1+ lymphocytes circulating in peripheral blood, but not the bulk or CD8+PD-1- cells, led to the direct enrichment of mutation-specific cells in three melanoma samples tested, with at least 1, 3 and 5 unique patient-specific neo-antigens recognized, respectively. The PD-1+ derived cells also displayed autologous tumor recognition. Furthermore, CD8+PD-1+ and PD-1hi cells isolated and expanded from the blood from a patient with colorectal cancer led to the identification of mutation-specific cells targeting two tumor neo-antigens. These findings provide a novel strategy to harness naturally-occuring mutation-specific T cells present in peripheral blood for the development of personalized T -cell based therapies to treat cancer.</jats:p>