While the origin of circulating PD-1+CD39+ CD4 T cells remains to be determined, the fact that they reflect an immune response to ongoing disease, i.e., to tumors in cancer patients, as shown here, is in agreement with data obtained in individuals with chronic viral infections [33], where circulating virus-specific CD39+PD-1+ CD8 T cells are detected. Here, ENTPD1 is linked to cancer.