Frontiers in Immunology (Sep 2023)

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

  • 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

DOI
https://doi.org/10.3389/fimmu.2023.1260492
Journal volume & issue
Vol. 14

Abstract

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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.

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