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Research ArticleClinical Studies

Smoking History Predicts High Presence of TILs and Efficacy of PD-1 Blockade in PD-L1 Expression-negative Non-small Cell Lung Cancer Patients

YUKIKO SHIMODA, TATSUYA YOSHIDA, MASAYUKI SHIRASAWA, TAKAAKI MIZUNO, HITOMI JO, YUJI MATSUMOTO, YUKI SHINNO, YUSUKE OKUMA, YASUSHI GOTO, HIDEHITO HORINOUCHI, NOBORU YAMAMOTO, YASUSHI YATABE, YUICHIRO OHE and NORIKO MOTOI
Anticancer Research November 2021, 41 (11) 5739-5747; DOI: https://doi.org/10.21873/anticanres.15390
YUKIKO SHIMODA
1Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan;
2Cancer Medicine, Cooperative Graduate School, The Jikei University Graduate School of Medicine, Tokyo, Japan;
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TATSUYA YOSHIDA
1Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan;
3Department of Experimental Therapeutics, National Cancer Center Hospital, Tokyo, Japan;
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  • For correspondence: tatyoshi@ncc.go.jp
MASAYUKI SHIRASAWA
1Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan;
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TAKAAKI MIZUNO
1Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan;
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HITOMI JO
1Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan;
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YUJI MATSUMOTO
1Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan;
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YUKI SHINNO
1Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan;
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YUSUKE OKUMA
1Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan;
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YASUSHI GOTO
1Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan;
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HIDEHITO HORINOUCHI
1Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan;
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NOBORU YAMAMOTO
1Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan;
3Department of Experimental Therapeutics, National Cancer Center Hospital, Tokyo, Japan;
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YASUSHI YATABE
4Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan
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YUICHIRO OHE
1Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan;
2Cancer Medicine, Cooperative Graduate School, The Jikei University Graduate School of Medicine, Tokyo, Japan;
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NORIKO MOTOI
4Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan
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Abstract

Background/Aim: Programmed death-ligand 1 (PD-L1) expression on tumor cells is a predictive biomarker of programmed cell death 1 (PD-1) blockade therapy. This study sought to clarify predictors of the efficacy of nivolumab in non-small cell lung cancer (NSCLC) patients with PD-L1 expression-negative tumors. Patients and Methods: We retrospectively reviewed the records of advanced NSCLC patients between January 2016 and April 2019, and investigated the predictive marker of nivolumab including the status of CD8+ tumor infiltrating lymphocytes (TILs). Results: A total of 70 NSCLC patients were included. Overall response rate (ORR) and progression-free survival (PFS) were better in patients with a heavy smoking history (smoking index: SI≥600) than in those without (SI<600) [ORR: 20.6% vs. 2.8%, (p=0.02), and PFS: 2.4 months vs. 1.8 months, (p=0.04)]. A high density of CD8+ TILs was significantly associated with a heavy smoking history (p=0.04). Conlusion: Heavy smoking history (SI≥600), which was correlated with a large number of CD8+ TILs, could be a predictor of the efficacy of nivolumab in NSCLC patients with PD-L1 expression-negative tumors.

Key Words:
  • Non-small cell lung cancer (NSCLC)
  • programmed death-ligand 1 (PD-L1)
  • smoking index
  • nivolumab
  • CD8+ tumor infiltrating lymphocytes (TILs)
  • Received September 7, 2021.
  • Revision received October 10, 2021.
  • Accepted October 11, 2021.
  • Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Anticancer Research: 41 (11)
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Smoking History Predicts High Presence of TILs and Efficacy of PD-1 Blockade in PD-L1 Expression-negative Non-small Cell Lung Cancer Patients
YUKIKO SHIMODA, TATSUYA YOSHIDA, MASAYUKI SHIRASAWA, TAKAAKI MIZUNO, HITOMI JO, YUJI MATSUMOTO, YUKI SHINNO, YUSUKE OKUMA, YASUSHI GOTO, HIDEHITO HORINOUCHI, NOBORU YAMAMOTO, YASUSHI YATABE, YUICHIRO OHE, NORIKO MOTOI
Anticancer Research Nov 2021, 41 (11) 5739-5747; DOI: 10.21873/anticanres.15390

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Smoking History Predicts High Presence of TILs and Efficacy of PD-1 Blockade in PD-L1 Expression-negative Non-small Cell Lung Cancer Patients
YUKIKO SHIMODA, TATSUYA YOSHIDA, MASAYUKI SHIRASAWA, TAKAAKI MIZUNO, HITOMI JO, YUJI MATSUMOTO, YUKI SHINNO, YUSUKE OKUMA, YASUSHI GOTO, HIDEHITO HORINOUCHI, NOBORU YAMAMOTO, YASUSHI YATABE, YUICHIRO OHE, NORIKO MOTOI
Anticancer Research Nov 2021, 41 (11) 5739-5747; DOI: 10.21873/anticanres.15390
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Keywords

  • Non-small cell lung cancer (NSCLC)
  • programmed death-ligand 1 (PD-L1)
  • smoking index
  • Nivolumab
  • CD8+ tumor infiltrating lymphocytes (TILs)
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