Greater extent of blood‐tumor TCR repertoire overlap is associated with favorable clinical responses to PD‐1 blockade. Issue 8 (22nd June 2021)

• Record Type: Journal Article
• Authors: Aoki, Hiroyasu; Ueha, Satoshi; Nakamura, Yoshiaki; Shichino, Shigeyuki; Nakajima, Hiromichi; Shimomura, Manami; Sato, Akihiro; Nakatsura, Tetsuya; Yoshino, Takayuki; Matsushima, Kouji
• Is Part Of: Cancer science. Volume 112:Issue 8(2021)
• Page Start: 2993
• Page End: 3004
• Publication Date: 2021-06-22
• Subjects: blood‐tumor overlapping clone -- immune checkpoint inhibitor -- PD‐1 blockade -- TCR repertoire; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.14975
• Languages: English
• ISSNs: 1347-9032

Abstract

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. Abstract : The T‐cell receptor repertoire of eight patients with gastrointestinal cancer treated with anti‐PD‐1 antibody (nivolumab) was analyzed. We focused on T‐cell clones that presented in both blood and tumor to analyze the tumor‐associated T‐cell clones in the blood. We found that responders to PD‐1 blockade tended to exhibit a higher total frequency of overlapping clones in the blood.