PD-1 blockade expands low-frequency T cells to enhance anti-tumor cytolytic activity in peripheral blood of advanced tumor patients

Immune therapies achieved clinical response successfully in many types of tumor. Understanding the regulation mechanisms of immune checkpoint inhibition would help improve clinical treatment. In this study, we explored the immunological responses with PD-1 blockade in advanced tumor patients using next-generation sequencing to quantify immune repertoire and transcriptome of immune cells in peripheral blood. We found PD-1 blockade remarkably facilitated non-specific low-frequency T cell clones expanding to enhance cytolytic activity of immune cells and apoptosis of these expanded T cell clones was suppressed comparing to the exhausted T cells at baseline. Furthermore, the apoptosis of immune cells made a prognostic significance in these patients. Therefore, PD-1 blockade expands low-frequency circulating T cell clones in peripheral blood that may disseminate and infiltrate to the tumor microenvironment to exert anti-tumor activity.