Novel quantitative immunohistochemical analysis for evaluating PD-L1 expression with phosphor-integrated dots for predicting the efficacy of patients with cancer treated with immune checkpoint inhibitors
IntroductionProgrammed cell death ligand 1 (PD-L1) expression in tumor tissues is measured as a predictor of the therapeutic efficacy of immune checkpoint inhibitors (ICIs) in many cancer types. PD-L1 expression is evaluated by immunohistochemical staining using 3,3´-diaminobenzidine (DAB) chronogen...
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1260492/full |
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| author | Ryotaro Ohkuma Ryotaro Ohkuma Sakiko Miura Satoshi Muto Yoshitaka Toyomasu Yuki Fujimoto Yuki Fujimoto Yuki Fujimoto Katsuaki Ieguchi Katsuaki Ieguchi Nobuyuki Onishi Nobuyuki Onishi Takashi Shimizu Takashi Shimizu Makoto Watanabe Makoto Watanabe Makoto Watanabe Makoto Watanabe Daisuke Takayanagi Daisuke Takayanagi Daisuke Takayanagi Tsubasa Goshima Tsubasa Goshima Tsubasa Goshima Atsushi Horiike Kazuyuki Hamada Hirotsugu Ariizumi Masahiro Shimokawa Yuya Hirasawa Tomoyuki Ishiguro Risako Suzuki Nana Iriguchi Toshiaki Tsurui Toshiaki Tsurui Toshiaki Tsurui Emiko Mura Sachiko Takenoshita Kazuki Numajiri Naoyuki Okabe Kiyoshi Yoshimura Kiyoshi Yoshimura Kiyoshi Yoshimura Mayumi Tsuji Yuji Kiuchi Yuji Kiuchi Toshiki Yajima Hideyuki Ishida Hiroyuki Suzuki Toshiko Yamochi Shinichi Kobayashi Takuya Tsunoda Satoshi Wada Satoshi Wada Satoshi Wada Satoshi Wada Satoshi Wada |
| author_facet | Ryotaro Ohkuma Ryotaro Ohkuma Sakiko Miura Satoshi Muto Yoshitaka Toyomasu Yuki Fujimoto Yuki Fujimoto Yuki Fujimoto Katsuaki Ieguchi Katsuaki Ieguchi Nobuyuki Onishi Nobuyuki Onishi Takashi Shimizu Takashi Shimizu Makoto Watanabe Makoto Watanabe Makoto Watanabe Makoto Watanabe Daisuke Takayanagi Daisuke Takayanagi Daisuke Takayanagi Tsubasa Goshima Tsubasa Goshima Tsubasa Goshima Atsushi Horiike Kazuyuki Hamada Hirotsugu Ariizumi Masahiro Shimokawa Yuya Hirasawa Tomoyuki Ishiguro Risako Suzuki Nana Iriguchi Toshiaki Tsurui Toshiaki Tsurui Toshiaki Tsurui Emiko Mura Sachiko Takenoshita Kazuki Numajiri Naoyuki Okabe Kiyoshi Yoshimura Kiyoshi Yoshimura Kiyoshi Yoshimura Mayumi Tsuji Yuji Kiuchi Yuji Kiuchi Toshiki Yajima Hideyuki Ishida Hiroyuki Suzuki Toshiko Yamochi Shinichi Kobayashi Takuya Tsunoda Satoshi Wada Satoshi Wada Satoshi Wada Satoshi Wada Satoshi Wada |
| author_sort | Ryotaro Ohkuma |
| collection | DOAJ |
| description | IntroductionProgrammed cell death ligand 1 (PD-L1) expression in tumor tissues is measured as a predictor of the therapeutic efficacy of immune checkpoint inhibitors (ICIs) in many cancer types. PD-L1 expression is evaluated by immunohistochemical staining using 3,3´-diaminobenzidine (DAB) chronogenesis (IHC-DAB); however, quantitative and reproducibility issues remain. We focused on a highly sensitive quantitative immunohistochemical method using phosphor-integrated dots (PIDs), which are fluorescent nanoparticles, and evaluated PD-L1 expression between the PID method and conventional DAB method.MethodsIn total, 155 patients with metastatic or recurrent cancer treated with ICIs were enrolled from four university hospitals. Tumor tissue specimens collected before treatment were subjected to immunohistochemical staining with both the PID and conventional DAB methods to evaluate PD-L1 protein expression.ResultsPD-L1 expression assessed using the PID and DAB methods was positively correlated. We quantified PD-L1 expression using the PID method and calculated PD-L1 PID scores. The PID score was significantly higher in the responder group than in the non-responder group. Survival analysis demonstrated that PD-L1 expression evaluated using the IHC-DAB method was not associated with progression-free survival (PFS) or overall survival (OS). Yet, PFS and OS were strikingly prolonged in the high PD-L1 PID score group.ConclusionQuantification of PD-L1 expression as a PID score was more effective in predicting the treatment efficacy and prognosis of patients with cancer treated with ICIs. The quantitative evaluation of PD-L1 expression using the PID method is a novel strategy for protein detection. It is highly significant that the PID method was able to identify a group of patients with a favorable prognosis who could not be identified by the conventional DAB method. |
| first_indexed | 2024-03-11T23:51:27Z |
| format | Article |
| id | doaj.art-ae7a3794a1b04272bd831501907f335c |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-11T23:51:27Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-ae7a3794a1b04272bd831501907f335c2023-09-19T07:06:34ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-09-011410.3389/fimmu.2023.12604921260492Novel quantitative immunohistochemical analysis for evaluating PD-L1 expression with phosphor-integrated dots for predicting the efficacy of patients with cancer treated with immune checkpoint inhibitorsRyotaro Ohkuma0Ryotaro Ohkuma1Sakiko Miura2Satoshi Muto3Yoshitaka Toyomasu4Yuki Fujimoto5Yuki Fujimoto6Yuki Fujimoto7Katsuaki Ieguchi8Katsuaki Ieguchi9Nobuyuki Onishi10Nobuyuki Onishi11Takashi Shimizu12Takashi Shimizu13Makoto Watanabe14Makoto Watanabe15Makoto Watanabe16Makoto Watanabe17Daisuke Takayanagi18Daisuke Takayanagi19Daisuke Takayanagi20Tsubasa Goshima21Tsubasa Goshima22Tsubasa Goshima23Atsushi Horiike24Kazuyuki Hamada25Hirotsugu Ariizumi26Masahiro Shimokawa27Yuya Hirasawa28Tomoyuki Ishiguro29Risako Suzuki30Nana Iriguchi31Toshiaki Tsurui32Toshiaki Tsurui33Toshiaki Tsurui34Emiko Mura35Sachiko Takenoshita36Kazuki Numajiri37Naoyuki Okabe38Kiyoshi Yoshimura39Kiyoshi Yoshimura40Kiyoshi Yoshimura41Mayumi Tsuji42Yuji Kiuchi43Yuji Kiuchi44Toshiki Yajima45Hideyuki Ishida46Hiroyuki Suzuki47Toshiko Yamochi48Shinichi Kobayashi49Takuya Tsunoda50Satoshi Wada51Satoshi Wada52Satoshi Wada53Satoshi Wada54Satoshi Wada55Division of Medical Oncology, Department of Medicine, School of Medicine, Showa University, Tokyo, JapanDepartment of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, JapanDepartment of Pathology, Showa University School of Medicine, Tokyo, JapanDepartment of Chest Surgery, School of Medicine, Fukushima Medical University, Fukushima, JapanDepartment of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Saitama, JapanDivision of Medical Oncology, Department of Medicine, School of Medicine, Showa University, Tokyo, JapanDepartment of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, JapanClinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, JapanDepartment of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, JapanClinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, JapanDepartment of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, JapanClinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, JapanDepartment of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, JapanClinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, JapanDepartment of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, JapanClinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, JapanDepartment of Pharmacology, School of Medicine, Showa University, Tokyo, JapanPharmacological Research Center, Showa University, Tokyo, JapanDivision of Medical Oncology, Department of Medicine, School of Medicine, Showa University, Tokyo, JapanDepartment of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, JapanClinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, JapanDivision of Medical Oncology, Department of Medicine, School of Medicine, Showa University, Tokyo, JapanDepartment of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, JapanClinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, JapanDivision of Medical Oncology, Department of Medicine, School of Medicine, Showa University, Tokyo, JapanDepartment of Chest Surgery, School of Medicine, Fukushima Medical University, Fukushima, JapanDivision of Medical Oncology, Department of Medicine, School of Medicine, Showa University, Tokyo, JapanDivision of Medical Oncology, Department of Medicine, School of Medicine, Showa University, Tokyo, JapanDivision of Medical Oncology, Department of Medicine, School of Medicine, Showa University, Tokyo, JapanDivision of Medical Oncology, Department of Medicine, School of Medicine, Showa University, Tokyo, JapanDivision of Medical Oncology, Department of Medicine, School of Medicine, Showa University, Tokyo, JapanDivision of Medical Oncology, Department of Medicine, School of Medicine, Showa University, Tokyo, JapanDivision of Medical Oncology, Department of Medicine, School of Medicine, Showa University, Tokyo, JapanDepartment of Pharmacology, School of Medicine, Showa University, Tokyo, JapanPharmacological Research Center, Showa University, Tokyo, JapanDivision of Medical Oncology, Department of Medicine, School of Medicine, Showa University, Tokyo, JapanClinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, JapanDepartment of General Surgical Science, Graduate School of Medicine, Gunma University, Gunma, JapanDepartment of Chest Surgery, School of Medicine, Fukushima Medical University, Fukushima, JapanDivision of Medical Oncology, Department of Medicine, School of Medicine, Showa University, Tokyo, JapanClinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan0Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, JapanPharmacological Research Center, Showa University, Tokyo, JapanDepartment of Pharmacology, School of Medicine, Showa University, Tokyo, JapanPharmacological Research Center, Showa University, Tokyo, Japan1Department of General Thoracic Surgery, Faculty of Medicine, Kagawa University, Kagawa, JapanDepartment of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Saitama, JapanDepartment of Chest Surgery, School of Medicine, Fukushima Medical University, Fukushima, JapanDepartment of Pathology, Showa University School of Medicine, Tokyo, JapanClinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, JapanDivision of Medical Oncology, Department of Medicine, School of Medicine, Showa University, Tokyo, JapanDivision of Medical Oncology, Department of Medicine, School of Medicine, Showa University, Tokyo, JapanDepartment of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, JapanClinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, JapanDepartment of Pharmacology, School of Medicine, Showa University, Tokyo, JapanPharmacological Research Center, Showa University, Tokyo, JapanIntroductionProgrammed cell death ligand 1 (PD-L1) expression in tumor tissues is measured as a predictor of the therapeutic efficacy of immune checkpoint inhibitors (ICIs) in many cancer types. PD-L1 expression is evaluated by immunohistochemical staining using 3,3´-diaminobenzidine (DAB) chronogenesis (IHC-DAB); however, quantitative and reproducibility issues remain. We focused on a highly sensitive quantitative immunohistochemical method using phosphor-integrated dots (PIDs), which are fluorescent nanoparticles, and evaluated PD-L1 expression between the PID method and conventional DAB method.MethodsIn total, 155 patients with metastatic or recurrent cancer treated with ICIs were enrolled from four university hospitals. Tumor tissue specimens collected before treatment were subjected to immunohistochemical staining with both the PID and conventional DAB methods to evaluate PD-L1 protein expression.ResultsPD-L1 expression assessed using the PID and DAB methods was positively correlated. We quantified PD-L1 expression using the PID method and calculated PD-L1 PID scores. The PID score was significantly higher in the responder group than in the non-responder group. Survival analysis demonstrated that PD-L1 expression evaluated using the IHC-DAB method was not associated with progression-free survival (PFS) or overall survival (OS). Yet, PFS and OS were strikingly prolonged in the high PD-L1 PID score group.ConclusionQuantification of PD-L1 expression as a PID score was more effective in predicting the treatment efficacy and prognosis of patients with cancer treated with ICIs. The quantitative evaluation of PD-L1 expression using the PID method is a novel strategy for protein detection. It is highly significant that the PID method was able to identify a group of patients with a favorable prognosis who could not be identified by the conventional DAB method.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1260492/fullphosphor-integrated dotsfluorescent nanoparticlesimmunohistochemistryimaging pathologyquantitative evaluationPD-L1 |
| spellingShingle | Ryotaro Ohkuma Ryotaro Ohkuma Sakiko Miura Satoshi Muto Yoshitaka Toyomasu Yuki Fujimoto Yuki Fujimoto Yuki Fujimoto Katsuaki Ieguchi Katsuaki Ieguchi Nobuyuki Onishi Nobuyuki Onishi Takashi Shimizu Takashi Shimizu Makoto Watanabe Makoto Watanabe Makoto Watanabe Makoto Watanabe Daisuke Takayanagi Daisuke Takayanagi Daisuke Takayanagi Tsubasa Goshima Tsubasa Goshima Tsubasa Goshima Atsushi Horiike Kazuyuki Hamada Hirotsugu Ariizumi Masahiro Shimokawa Yuya Hirasawa Tomoyuki Ishiguro Risako Suzuki Nana Iriguchi Toshiaki Tsurui Toshiaki Tsurui Toshiaki Tsurui Emiko Mura Sachiko Takenoshita Kazuki Numajiri Naoyuki Okabe Kiyoshi Yoshimura Kiyoshi Yoshimura Kiyoshi Yoshimura Mayumi Tsuji Yuji Kiuchi Yuji Kiuchi Toshiki Yajima Hideyuki Ishida Hiroyuki Suzuki Toshiko Yamochi Shinichi Kobayashi Takuya Tsunoda Satoshi Wada Satoshi Wada Satoshi Wada Satoshi Wada Satoshi Wada Novel quantitative immunohistochemical analysis for evaluating PD-L1 expression with phosphor-integrated dots for predicting the efficacy of patients with cancer treated with immune checkpoint inhibitors Frontiers in Immunology phosphor-integrated dots fluorescent nanoparticles immunohistochemistry imaging pathology quantitative evaluation PD-L1 |
| title | Novel quantitative immunohistochemical analysis for evaluating PD-L1 expression with phosphor-integrated dots for predicting the efficacy of patients with cancer treated with immune checkpoint inhibitors |
| title_full | Novel quantitative immunohistochemical analysis for evaluating PD-L1 expression with phosphor-integrated dots for predicting the efficacy of patients with cancer treated with immune checkpoint inhibitors |
| title_fullStr | Novel quantitative immunohistochemical analysis for evaluating PD-L1 expression with phosphor-integrated dots for predicting the efficacy of patients with cancer treated with immune checkpoint inhibitors |
| title_full_unstemmed | Novel quantitative immunohistochemical analysis for evaluating PD-L1 expression with phosphor-integrated dots for predicting the efficacy of patients with cancer treated with immune checkpoint inhibitors |
| title_short | Novel quantitative immunohistochemical analysis for evaluating PD-L1 expression with phosphor-integrated dots for predicting the efficacy of patients with cancer treated with immune checkpoint inhibitors |
| title_sort | novel quantitative immunohistochemical analysis for evaluating pd l1 expression with phosphor integrated dots for predicting the efficacy of patients with cancer treated with immune checkpoint inhibitors |
| topic | phosphor-integrated dots fluorescent nanoparticles immunohistochemistry imaging pathology quantitative evaluation PD-L1 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1260492/full |
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