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Research ArticleExperimental Studies

Tumor PD-L1 and VEGF Expression, and CD8 T Cell Infiltration Predict Clinical Response to Immune Checkpoint Inhibitors in Non-small Cell Lung Cancer

YUJI NOJIMA, KATSUHIKO SHIMIZU, SHINSUKE SAISHO, AI MAEDA, TAKESHI KUROSAKI, KOJI KUROSE, TORU OGA, MIKIO OKA and MASAO NAKATA
Anticancer Research November 2021, 41 (11) 5469-5475; DOI: https://doi.org/10.21873/anticanres.15359
YUJI NOJIMA
1Department of General Thoracic Surgery, Kawasaki Medical School, Okayama, Japan;
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KATSUHIKO SHIMIZU
1Department of General Thoracic Surgery, Kawasaki Medical School, Okayama, Japan;
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  • For correspondence: kshimizu@med.kawasaki-m.ac.jp
SHINSUKE SAISHO
1Department of General Thoracic Surgery, Kawasaki Medical School, Okayama, Japan;
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AI MAEDA
1Department of General Thoracic Surgery, Kawasaki Medical School, Okayama, Japan;
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TAKESHI KUROSAKI
1Department of General Thoracic Surgery, Kawasaki Medical School, Okayama, Japan;
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KOJI KUROSE
2Department of Respiratory Medicine, Kawasaki Medical School, Okayama, Japan;
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TORU OGA
2Department of Respiratory Medicine, Kawasaki Medical School, Okayama, Japan;
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MIKIO OKA
3Department of Immuno-Oncology, Kawasaki Medical School, Okayama, Japan
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MASAO NAKATA
1Department of General Thoracic Surgery, Kawasaki Medical School, Okayama, Japan;
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Abstract

Background/Aim: We evaluated the efficacy of “the tumor immune microenvironment (TIME) classification” for predicting clinical response to immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer (NSCLC). In addition, we aimed to evaluate the “modified TIME classification”, which adds the vascular endothelial growth factor (VEGF) status to TIME. Materials and Methods: Programmed cell death receptor ligand-1 (PD-L1), CD8 T cell tumor-infiltrating lymphocytes (CD8+TILs) count and VEGF expression analyses were performed using immuno - histochemistry in 44 patients who had undergone ICI monotherapy. Results: Regarding TIME classification, type-I (PD-L1 high and CD8+TILs high) had a significantly higher response than the other types. Using the modified TIME classification, type-IA (PD-L1 high, CD8+TILs high, and VEGF low) had a significantly higher response than the other types. Conclusion: The modified TIME classification, which adds tumor VEGF expression to “the TIME classification”, could be useful in predicting clinical response to ICI monotherapy.

Key Words:
  • Tumor immune microenvironment
  • immune checkpoint inhibitor
  • non-small cell lung cancer
  • vascular endothelial growth factor
  • biomarker
  • Received May 30, 2021.
  • Revision received October 11, 2021.
  • Accepted October 12, 2021.
  • Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Anticancer Research: 41 (11)
Anticancer Research
Vol. 41, Issue 11
November 2021
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Tumor PD-L1 and VEGF Expression, and CD8 T Cell Infiltration Predict Clinical Response to Immune Checkpoint Inhibitors in Non-small Cell Lung Cancer
YUJI NOJIMA, KATSUHIKO SHIMIZU, SHINSUKE SAISHO, AI MAEDA, TAKESHI KUROSAKI, KOJI KUROSE, TORU OGA, MIKIO OKA, MASAO NAKATA
Anticancer Research Nov 2021, 41 (11) 5469-5475; DOI: 10.21873/anticanres.15359

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Tumor PD-L1 and VEGF Expression, and CD8 T Cell Infiltration Predict Clinical Response to Immune Checkpoint Inhibitors in Non-small Cell Lung Cancer
YUJI NOJIMA, KATSUHIKO SHIMIZU, SHINSUKE SAISHO, AI MAEDA, TAKESHI KUROSAKI, KOJI KUROSE, TORU OGA, MIKIO OKA, MASAO NAKATA
Anticancer Research Nov 2021, 41 (11) 5469-5475; DOI: 10.21873/anticanres.15359
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Keywords

  • Tumor immune microenvironment
  • immune checkpoint inhibitor
  • Non-small cell lung cancer
  • vascular endothelial growth factor
  • biomarker
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