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

Immunology

Shinichi Kobayashi¹  Sachiko Takenoshita¹  Satoshi Muto²  Naoyuki Okabe²  Hiroyuki Suzuki²  Kazuyuki Hamada²  Takashi Shimizu³  Katsuaki Ieguchi³  Nobuyuki Onishi³  Makoto Watanabe⁴  Hideyuki Ishida⁵  Yoshitaka Toyomasu⁵  Kazuki Numajiri⁶  Toshiki Yajima⁷  Toshiko Yamochi⁸  Sakiko Miura⁸  Yuji Kiuchi⁹  Risako Suzuki^1,10  Masahiro Shimokawa^1,10  Takuya Tsunoda^1,10  Tomoyuki Ishiguro^1,10  Yuya Hirasawa^1,10  Emiko Mura^1,10  Nana Iriguchi^1,10  Hirotsugu Ariizumi^1,10  Atsushi Horiike^1,10  Kiyoshi Yoshimura^1,11  Ryotaro Ohkuma^1,12  Yuki Fujimoto^1,13  Tsubasa Goshima^1,13  Daisuke Takayanagi^1,13  Satoshi Wada^1,14  Toshiaki Tsurui^1,15  Mayumi Tsuji^1,16 

[1] Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan;Department of Chest Surgery, School of Medicine, Fukushima Medical University, Fukushima, 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 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;Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Saitama, Japan;Department of General Surgical Science, Graduate School of Medicine, Gunma University, Gunma, Japan;Department of General Thoracic Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan;Department of Pathology, Showa University School of Medicine, Tokyo, Japan;Department of Pharmacology, School of Medicine, Showa University, Tokyo, Japan;Pharmacological Research Center, Showa University, Tokyo, Japan;Division of Medical Oncology, Department of Medicine, School of Medicine, Showa University, Tokyo, Japan;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;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;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;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;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;Pharmacological Research Center, Showa University, Tokyo, Japan;

关键词: phosphor-integrated dots;    fluorescent nanoparticles;    immunohistochemistry;    imaging pathology;    quantitative evaluation;    PD-L1;    immune-checkpoint inhibitors;    biomarker;   

DOI  :  10.3389/fimmu.2023.1260492

 received in 2023-07-17, accepted in 2023-09-04,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
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