Increased Plasma Soluble PD-1 Concentration Correlates with Disease Progression in Patients with Cancer Treated with Anti-PD-1 Antibodies
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, t...
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| Format: | Article |
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MDPI AG
2021-12-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/12/1929 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Ryotaro Ohkuma |
| collection | DOAJ |
| description | 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 (<i>p</i> = 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 (<i>p</i> = 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. |
| first_indexed | 2024-03-10T04:33:28Z |
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| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T04:33:28Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
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| series | Biomedicines |
| spelling | doaj.art-233a7fcb10684854adad9aa44c898b582023-11-23T03:57:46ZengMDPI AGBiomedicines2227-90592021-12-01912192910.3390/biomedicines9121929Increased Plasma Soluble PD-1 Concentration Correlates with Disease Progression in Patients with Cancer Treated with Anti-PD-1 AntibodiesRyotaro Ohkuma0Katsuaki Ieguchi1Makoto Watanabe2Daisuke Takayanagi3Tsubasa Goshima4Rie Onoue5Kazuyuki Hamada6Yutaro Kubota7Atsushi Horiike8Tomoyuki Ishiguro9Yuya Hirasawa10Hirotsugu Ariizumi11Junji Tsurutani12Kiyoshi Yoshimura13Mayumi Tsuji14Yuji Kiuchi15Shinichi Kobayashi16Takuya Tsunoda17Satoshi Wada18Department of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology & Therapeutics, Showa University, 6-11-11, Kitakarasuyama, Setagaya-ku, Tokyo 157-8577, JapanDepartment of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology & Therapeutics, Showa University, 6-11-11, Kitakarasuyama, Setagaya-ku, Tokyo 157-8577, JapanDepartment of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology & Therapeutics, Showa University, 6-11-11, Kitakarasuyama, Setagaya-ku, Tokyo 157-8577, JapanDepartment of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology & Therapeutics, Showa University, 6-11-11, Kitakarasuyama, Setagaya-ku, Tokyo 157-8577, JapanDepartment of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology & Therapeutics, Showa University, 6-11-11, Kitakarasuyama, Setagaya-ku, Tokyo 157-8577, JapanDepartment of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology & Therapeutics, Showa University, 6-11-11, Kitakarasuyama, Setagaya-ku, Tokyo 157-8577, JapanDepartment of Medicine, Division of Medical Oncology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8555, JapanDepartment of Medicine, Division of Medical Oncology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8555, JapanDepartment of Medicine, Division of Medical Oncology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8555, JapanDepartment of Medicine, Division of Medical Oncology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8555, JapanDepartment of Medicine, Division of Medical Oncology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8555, JapanDepartment of Medicine, Division of Medical Oncology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8555, JapanDepartment of Medicine, Division of Medical Oncology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8555, JapanDepartment of Medicine, Division of Medical Oncology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8555, JapanDepartment of Pharmacology, Division of Medical Pharmacology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8555, JapanDepartment of Pharmacology, Division of Medical Pharmacology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8555, JapanClinical Research Institute for Clinical Pharmacology & Therapeutics, Showa University, 6-11-11, Kitakarasuyama, Setagaya-ku, Tokyo 157-8577, JapanDepartment of Medicine, Division of Medical Oncology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8555, JapanDepartment of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology & Therapeutics, Showa University, 6-11-11, Kitakarasuyama, Setagaya-ku, Tokyo 157-8577, JapanImmune 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 (<i>p</i> = 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 (<i>p</i> = 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.https://www.mdpi.com/2227-9059/9/12/1929biomarkersimmune checkpoint inhibitorsanti-programmed death-1 (PD-1) |
| spellingShingle | 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 Increased Plasma Soluble PD-1 Concentration Correlates with Disease Progression in Patients with Cancer Treated with Anti-PD-1 Antibodies Biomedicines biomarkers immune checkpoint inhibitors anti-programmed death-1 (PD-1) |
| title | Increased Plasma Soluble PD-1 Concentration Correlates with Disease Progression in Patients with Cancer Treated with Anti-PD-1 Antibodies |
| title_full | Increased Plasma Soluble PD-1 Concentration Correlates with Disease Progression in Patients with Cancer Treated with Anti-PD-1 Antibodies |
| title_fullStr | Increased Plasma Soluble PD-1 Concentration Correlates with Disease Progression in Patients with Cancer Treated with Anti-PD-1 Antibodies |
| title_full_unstemmed | Increased Plasma Soluble PD-1 Concentration Correlates with Disease Progression in Patients with Cancer Treated with Anti-PD-1 Antibodies |
| title_short | Increased Plasma Soluble PD-1 Concentration Correlates with Disease Progression in Patients with Cancer Treated with Anti-PD-1 Antibodies |
| title_sort | increased plasma soluble pd 1 concentration correlates with disease progression in patients with cancer treated with anti pd 1 antibodies |
| topic | biomarkers immune checkpoint inhibitors anti-programmed death-1 (PD-1) |
| url | https://www.mdpi.com/2227-9059/9/12/1929 |
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