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Biphasic prognostic significance of PD-L1 expression status in patients with early- and locally advanced-stage non-small cell lung cancer

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Abstract

Programmed cell death-ligand 1 (PD-L1) expression on tumor cells is induced by interferon-gamma, suggesting the induction of an anti-tumor immune response. In turn, binding of PD-L1 to programmed cell death 1 (PD-1) triggers an immune checkpoint pathway that contributes to tumor growth. Though it remains to be elucidated, the clinical significance of PD-L1 expression might vary with tumor progression in non–small-cell lung cancer (NSCLC). Immunohistochemical analysis of PD-L1 was done in tumor specimens from patients who underwent radical surgery for stage I–IIIA NSCLC (n = 228). Tumor PD-L1 expression intensity was semi-quantitatively scored and its correlation with various clinicopathological features and postoperative relapse-free survival (RFS) was assessed relative to pathological stage. In stage I, postoperative RFS was significantly prolonged in patients with a high PD-L1 score compared with a low PD-L1 score, exhibiting 5-year relapse-free probabilities of 94.1% and 75.1%, respectively (P = 0.031). A multivariate analysis revealed that a high PD-L1 score was a prognostic factor of longer postoperative RFS (hazard ratio: 0.111, P = 0.033). Conversely, in stages II and IIIA, patients with a high PD-L1 score tended to suffer from postoperative tumor recurrence. In early-stage NSCLC, high tumor PD-L1 expression status represents a biomarker to predict good prognosis after radical surgery and may reflect the induction of an antitumor immune response. However, in locally advanced stage NSCLC, tumor PD-L1 expression status may reflect the execution of an immune checkpoint pathway and predicts the incidence of postoperative tumor recurrence.

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Abbreviations

NSCLC:

Non–small-cell lung cancer

OS:

Overall survival

PD-L1:

Programmed cell death-ligand 1

RFS:

Relapse-free survival

5-y RFP:

5-Year relapse-free probability

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Acknowledgements

This work was supported in part by Grant-in-Aid for Scientific Research from The Japan Society for the Promotion of Science (JSPS KAKENHI Grant Number: 16K10677, 16H06277, 17K10780, and 19H03559). K.T. and Y.D. are members of Shiga Cancer Treatment Project supported by Shiga Prefecture (Japan) and IMSUT (Institute of Medical Sciences, The University of Tokyo) Joint Research Project FY2016-2021.

Funding

This work was supported in part by Grant-in-Aid for Scientific Research from The Japan Society for the Promotion of Science (JSPS KAKENHI Grant Number: 16K10677, 16H06277, 17K10780, and 19H03559).

Author information

Authors and Affiliations

  1. Department of Medical Oncology and Cancer Center, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, Shiga, 520-2192, Japan

    Koji Teramoto, Hidetoshi Sumimoto & Yataro Daigo

  2. Center for Advanced Medicine Against Cancer, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, Shiga, 520-2192, Japan

    Koji Teramoto, Hidetoshi Sumimoto & Yataro Daigo

  3. Center for Antibody and Vaccine Therapy, Research Hospital, Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan

    Koji Teramoto & Yataro Daigo

  4. Department of Surgery, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, Shiga, 520-2192, Japan

    Tomoyuki Igarashi, Yoko Kataoka & Jun Hanaoka

  5. Department of Pathology and Laboratory Medicine, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka, 573-1010, Japan

    Mitsuaki Ishida

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  1. Koji Teramoto
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  2. Tomoyuki Igarashi
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Contributions

KT: Conceptualization, Methodology, Formal analysis, Investigation, Data curation, Writing-Original draft, Project administration, Funding acquisition. TI: Validation, Investigation, Writing-Original draft, Funding acquisition. YK: Validation, Investigation. MI: Validation, Investigation. JH: Resources. HS: Supervision. YD: Supervision, Writing-Review and Editing, Funding acquisition.

Corresponding authors

Correspondence to Koji Teramoto or Yataro Daigo.

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The authors have no conflicts of interest.

Ethical approval

The study design was approved by the Ethical Committee of Shiga University of Medical Science (approval number: R2016-115).

Informed consent

Informed consent was obtained from all patients in the study. The patients agreed to the use of their specimens and clinical data for research and publication.

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Teramoto, K., Igarashi, T., Kataoka, Y. et al. Biphasic prognostic significance of PD-L1 expression status in patients with early- and locally advanced-stage non-small cell lung cancer. Cancer Immunol Immunother 70, 1063–1074 (2021). https://doi.org/10.1007/s00262-020-02755-w

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  • DOI: https://doi.org/10.1007/s00262-020-02755-w

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