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

doi:10.3390/biomedicines9121929

Biomedicines (Dec 2021)

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

DOI: https://doi.org/10.3390/biomedicines9121929
Journal volume & issue: Vol. 9, no. 12
p. 1929

Abstract

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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.

Published in Biomedicines

ISSN: 2227-9059 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Biology (General)
Website: http://www.mdpi.com/journal/biomedicines

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