Open AccessGreater extent of blood‐tumor TCR repertoire overlap is associated with favorable clinical responses to PD‐1 blockade
Author(s) -
Aoki Hiroyasu,
Ueha Satoshi,
Nakamura Yoshiaki,
Shichino Shigeyuki,
Nakajima Hiromichi,
Shimomura Manami,
Sato Akihiro,
Nakatsura Tetsuya,
Yoshino Takayuki,
Matsushima Kouji
Publication year - 2021
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14975
Subject(s) - blockade , t cell receptor , repertoire , nivolumab , cd8 , immunology , antibody , biomarker , t cell , biology , medicine , antigen , cancer research , immune system , oncology , receptor , immunotherapy , genetics , acoustics , physics
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.