2-B-YIA5-5
<title_ja>Nivolumab治療における制御性T細胞のNivolumab–PD-1受容体占拠率は治療反応性を予測する</title_ja>
<title_en>Nivolumab receptor occupancy on effector regulatory T cells predicts clinical benefit</title_en>
〇細沼 雅弘1,2,3,4、平澤 優弥4、倉増 敦朗2、馬場 勇太2、鶴井 敏光1,2,3、角田 卓也4、木内 祐二1,2,3、吉村 清2,4
Hosonuma Masahiro1,2,3,4, Yuya Hirasawa4, Atsuo Kuramasu2, Yuta Baba2, Toshiaki Tsurui1,2,3, Takuya Tsunoda4, Yuji Kiuchi1,2,3, Kiyoshi Yoshimura2,4
1昭和大・医・薬理学講座 医科薬理学部門、2昭和大・臨床薬理研究所・臨床免疫腫瘍学部門、3昭和大・薬理科学研究センター、4昭和大・医・部内科学講座腫瘍内科学部門
1Division of Medical Pharmacology, Department of Pharmacology, Showa University School of Medicine, 2Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, 3Pharmacological Research Center, Showa University, 4Division of Medical Oncology, Department of Medicine, Showa University School of Medicine
Immune checkpoint inhibitor discovery represents a turning point in cancer treatment. However, the response rates of solid tumors remain approximately 10%–30%; consequently, prognostic and immune-related adverse event (irAE) predictors are being explored. The programmed cell death protein 1 (PD-1) receptor occupancy (RO) of PD-1 inhibitors depends on the number of peripheral blood lymphocytes and their PD-1 expression levels, suggesting that the RO may be related to efficacy and adverse events. As PD-1 inhibition affects each T-cell subset differently, the RO of each cell population must be characterized. However, relevant data have not been reported, and the prognostic relevance of this parameter is not known. In this study, we aimed to clarify the association between the nivolumab RO in each T-cell population and patient prognosis and reveal the development of irAEs in nivolumab-treated patients. Thirty-two patients were included in the study, and the mean follow-up period was 364 days. The nivolumab RO on effector regulatory T cells (eTregs) was significantly lower in the group that presented clinical benefits, and a significant negative association was observed between PD-1 occupancy on eTregs and all-cause mortality. The results suggest that the nivolumab RO on eTregs may be a prognostic factor in PD-1 inhibitor therapy, implying that the inhibition of PD-1/PD-ligand 1 (PD-L1) signaling on eTregs may attenuate antitumor effects.