Greater extent of blood-tumor TCR repertoire overlap is associated with favorable clinical responses to PD-1 blockade

Abstract

With the widespread use of programmed death receptor-1 (PD-1) blockade therapy, sensitive and specific predictive biomarkers that guide patient selection are urgently needed. T-cell receptor (TCR) repertoire, which reflects antitumor T-cell responses based on antigen specificity, is expected as a novel biomarker for PD-1 blockade therapy. In the present study, the TCR repertoire of eight patients with gastrointestinal cancer treated with anti-PD-1 antibody (nivolumab) was analyzed. To analyze the tumor-associated T-cell clones in the blood and their mobilization into the tumor, we focused on T-cell clones that presented in both blood and tumor (blood-tumor overlapping clones). Responders to PD-1 blockade tended to exhibit a higher number of overlapping clones in the tumor and a higher total frequency in the blood. Moreover, a higher total frequency of overlapping clones in blood CD8⁺ T cells before treatment was associated with a favorable clinical response. Collectively, these results suggest the possibility of blood-tumor TCR repertoire overlap to predict clinical response to PD-1 blockade and guide patient selection before the treatment.

Keywords: PD-1 blockade; TCR repertoire; blood-tumor overlapping clone; immune checkpoint inhibitor.