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.

Autor:	Ohkuma R; Division of Medical Oncology, Department of Medicine, School of Medicine, Showa University, Tokyo, Japan.; Department of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan., Miura S; Department of Pathology, Showa University School of Medicine, Tokyo, Japan., Muto S; Department of Chest Surgery, School of Medicine, Fukushima Medical University, Fukushima, Japan., Toyomasu Y; Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Saitama, Japan., Fujimoto Y; Division of Medical Oncology, Department of Medicine, School of Medicine, Showa University, Tokyo, Japan.; Department of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan.; Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan., Ieguchi K; Department of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan.; Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan., Onishi N; Department of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan.; Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan., Shimizu T; Department of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan.; Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan., Watanabe M; Department of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan.; Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan.; Department of Pharmacology, School of Medicine, Showa University, Tokyo, Japan.; Pharmacological Research Center, Showa University, Tokyo, Japan., Takayanagi D; Division of Medical Oncology, Department of Medicine, School of Medicine, Showa University, Tokyo, Japan.; Department of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan.; Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan., Goshima T; Division of Medical Oncology, Department of Medicine, School of Medicine, Showa University, Tokyo, Japan.; Department of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan.; Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan., Horiike A; Division of Medical Oncology, Department of Medicine, School of Medicine, Showa University, Tokyo, Japan., Hamada K; Department of Chest Surgery, School of Medicine, Fukushima Medical University, Fukushima, Japan., Ariizumi H; Division of Medical Oncology, Department of Medicine, School of Medicine, Showa University, Tokyo, Japan., Shimokawa M; Division of Medical Oncology, Department of Medicine, School of Medicine, Showa University, Tokyo, Japan., Hirasawa Y; Division of Medical Oncology, Department of Medicine, School of Medicine, Showa University, Tokyo, Japan., Ishiguro T; Division of Medical Oncology, Department of Medicine, School of Medicine, Showa University, Tokyo, Japan., Suzuki R; Division of Medical Oncology, Department of Medicine, School of Medicine, Showa University, Tokyo, Japan., Iriguchi N; Division of Medical Oncology, Department of Medicine, School of Medicine, Showa University, Tokyo, Japan., Tsurui T; Division of Medical Oncology, Department of Medicine, School of Medicine, Showa University, Tokyo, Japan.; Department of Pharmacology, School of Medicine, Showa University, Tokyo, Japan.; Pharmacological Research Center, Showa University, Tokyo, Japan., Mura E; Division of Medical Oncology, Department of Medicine, School of Medicine, Showa University, Tokyo, Japan., Takenoshita S; Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan., Numajiri K; Department of General Surgical Science, Graduate School of Medicine, Gunma University, Gunma, Japan., Okabe N; Department of Chest Surgery, School of Medicine, Fukushima Medical University, Fukushima, Japan., Yoshimura K; Division of Medical Oncology, Department of Medicine, School of Medicine, Showa University, Tokyo, Japan.; Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan.; Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan., Tsuji M; Pharmacological Research Center, Showa University, Tokyo, Japan., Kiuchi Y; Department of Pharmacology, School of Medicine, Showa University, Tokyo, Japan.; Pharmacological Research Center, Showa University, Tokyo, Japan., Yajima T; Department of General Thoracic Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan., Ishida H; Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Saitama, Japan., Suzuki H; Department of Chest Surgery, School of Medicine, Fukushima Medical University, Fukushima, Japan., Yamochi T; Department of Pathology, Showa University School of Medicine, Tokyo, Japan., Kobayashi S; Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan., Tsunoda T; Division of Medical Oncology, Department of Medicine, School of Medicine, Showa University, Tokyo, Japan., Wada S; Division of Medical Oncology, Department of Medicine, School of Medicine, Showa University, Tokyo, Japan.; Department of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan.; Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan.; Department of Pharmacology, School of Medicine, Showa University, Tokyo, Japan.; Pharmacological Research Center, Showa University, Tokyo, Japan.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2023 Sep 18; Vol. 14, pp. 1260492. Date of Electronic Publication: 2023 Sep 18 (Print Publication: 2023).
DOI:	10.3389/fimmu.2023.1260492
Abstrakt:	Introduction: Programmed 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. Methods: In 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. Results: PD-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. Conclusion: Quantification 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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from Konica Minolta, Inc. (Tokyo, Japan). The funder had the following involvement in the study: methodology and software. The QUIK software used for data analysis in the present study was also supplied by this company. (Copyright © 2023 Ohkuma, Miura, Muto, Toyomasu, Fujimoto, Ieguchi, Onishi, Shimizu, Watanabe, Takayanagi, Goshima, Horiike, Hamada, Ariizumi, Shimokawa, Hirasawa, Ishiguro, Suzuki, Iriguchi, Tsurui, Mura, Takenoshita, Numajiri, Okabe, Yoshimura, Tsuji, Kiuchi, Yajima, Ishida, Suzuki, Yamochi, Kobayashi, Tsunoda and Wada.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu