Increased Plasma Soluble PD-1 Concentration Correlates with Disease Progression in Patients with Cancer Treated with Anti-PD-1 Antibodies
Ryotaro Ohkuma,
Katsuaki Ieguchi,
Makoto Watanabe,
Daisuke Takayanagi,
Tsubasa Goshima,
Rie Onoue,
Kazuyuki Hamada,
Yutaro Kubota,
Atsushi Horiike,
Tomoyuki Ishiguro,
Yuya Hirasawa,
Hirotsugu Ariizumi,
Junji Tsurutani,
Kiyoshi Yoshimura,
Mayumi Tsuji,
Yuji Kiuchi,
Shinichi Kobayashi,
Takuya Tsunoda,
Satoshi Wada
Affiliations
Ryotaro Ohkuma
Department of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology & Therapeutics, Showa University, 6-11-11, Kitakarasuyama, Setagaya-ku, Tokyo 157-8577, Japan
Katsuaki Ieguchi
Department of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology & Therapeutics, Showa University, 6-11-11, Kitakarasuyama, Setagaya-ku, Tokyo 157-8577, Japan
Makoto Watanabe
Department of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology & Therapeutics, Showa University, 6-11-11, Kitakarasuyama, Setagaya-ku, Tokyo 157-8577, Japan
Daisuke Takayanagi
Department of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology & Therapeutics, Showa University, 6-11-11, Kitakarasuyama, Setagaya-ku, Tokyo 157-8577, Japan
Tsubasa Goshima
Department of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology & Therapeutics, Showa University, 6-11-11, Kitakarasuyama, Setagaya-ku, Tokyo 157-8577, Japan
Rie Onoue
Department of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology & Therapeutics, Showa University, 6-11-11, Kitakarasuyama, Setagaya-ku, Tokyo 157-8577, Japan
Kazuyuki Hamada
Department of Medicine, Division of Medical Oncology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
Yutaro Kubota
Department of Medicine, Division of Medical Oncology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
Atsushi Horiike
Department of Medicine, Division of Medical Oncology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
Tomoyuki Ishiguro
Department of Medicine, Division of Medical Oncology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
Yuya Hirasawa
Department of Medicine, Division of Medical Oncology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
Hirotsugu Ariizumi
Department of Medicine, Division of Medical Oncology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
Junji Tsurutani
Department of Medicine, Division of Medical Oncology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
Kiyoshi Yoshimura
Department of Medicine, Division of Medical Oncology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
Mayumi Tsuji
Department of Pharmacology, Division of Medical Pharmacology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
Yuji Kiuchi
Department of Pharmacology, Division of Medical Pharmacology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
Shinichi Kobayashi
Clinical Research Institute for Clinical Pharmacology & Therapeutics, Showa University, 6-11-11, Kitakarasuyama, Setagaya-ku, Tokyo 157-8577, Japan
Takuya Tsunoda
Department of Medicine, Division of Medical Oncology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
Satoshi Wada
Department of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology & Therapeutics, Showa University, 6-11-11, Kitakarasuyama, Setagaya-ku, Tokyo 157-8577, Japan
Immune checkpoint inhibitors (ICIs) confer remarkable therapeutic benefits to patients with various cancers. However, many patients are non-responders or develop resistance following an initial response to ICIs. There are no reliable biomarkers to predict the therapeutic effect of ICIs. Therefore, this study investigated the clinical implications of plasma levels of soluble anti-programmed death-1 (sPD-1) in patients with cancer treated with ICIs. In total, 22 patients (13 with non-small-cell lung carcinoma, 8 with gastric cancer, and 1 with bladder cancer) were evaluated for sPD-1 concentration using enzyme-linked immunosorbent assays for diagnostic and anti-PD-1 antibody analyses. sPD-1 levels were low before the administration of anti-PD-1 antibodies. After two and four cycles of anti-PD-1 antibody therapy, sPD-1 levels significantly increased compared with pretreatment levels (p = 0.0348 vs. 0.0232). We observed an increased rate of change in plasma sPD-1 concentrations after two and four cycles of anti-PD-1 antibody therapy that significantly correlated with tumor size progression (p = 0.024). sPD-1 may be involved in resistance to anti-PD-1 antibody therapy, suggesting that changes in sPD-1 levels can identify primary ICI non-responders early in treatment. Detailed analysis of each cancer type revealed the potential of sPD-1 as a predictive biomarker of response to ICI treatment in patients with cancer.
