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Research ArticleExperimental Studies

STAT3 Contributes a Favorable Response to Pembrolizumab Through IFN-γ-induced Apoptosis in Urothelial Cancer

HIROTAKA FUCHIZAWA, KIYOHIRO ANDO, NORIKO MOTOI, TOSHIHIKO IIZUKA, MASAHARU INOUE, KOUKI MITANI, YUTA SANO, HISANORI TAKENOBU, MASAYUKI HARUTA, RITSUKO ONUKI, YOH MATSUOKA, TAKEHIKO KAMIJO and YUKIO KAGEYAMA
Anticancer Research May 2024, 44 (5) 1925-1930; DOI: https://doi.org/10.21873/anticanres.16994
HIROTAKA FUCHIZAWA
1Department of Urology, Saitama Cancer Center, Saitama, Japan;
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KIYOHIRO ANDO
2Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama, Japan;
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  • For correspondence: kiyohiro_ando@saitama-pho.jp
NORIKO MOTOI
3Department of Pathology, Saitama Cancer Center, Saitama, Japan
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TOSHIHIKO IIZUKA
3Department of Pathology, Saitama Cancer Center, Saitama, Japan
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MASAHARU INOUE
1Department of Urology, Saitama Cancer Center, Saitama, Japan;
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KOUKI MITANI
1Department of Urology, Saitama Cancer Center, Saitama, Japan;
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YUTA SANO
1Department of Urology, Saitama Cancer Center, Saitama, Japan;
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HISANORI TAKENOBU
2Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama, Japan;
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MASAYUKI HARUTA
2Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama, Japan;
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RITSUKO ONUKI
2Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama, Japan;
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YOH MATSUOKA
1Department of Urology, Saitama Cancer Center, Saitama, Japan;
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TAKEHIKO KAMIJO
2Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama, Japan;
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YUKIO KAGEYAMA
1Department of Urology, Saitama Cancer Center, Saitama, Japan;
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Abstract

Background/Aim: Pembrolizumab, a second-line therapy for platinum-refractory advanced urothelial carcinoma (UC), is needed to improve objective response rate. Hence, it is crucial to identify optimal predictive biomarkers of responses. This study aimed to clarify the predictive value and role of signal transducer and activator of transcription 3 (STAT3) in selecting patients with advanced UC who might benefit clinically from pembrolizumab therapy. Patients and Methods: We retrospectively analyzed 31 patients who received pembrolizumab therapy for UC. STAT3, phosphorylated STAT3 (p-STAT3), and PD-L1 expression were determined using tissue microarrays constructed from patient-derived specimens, and the association of these expression levels with overall survival was analyzed. We assessed the functional role of STAT3 in bladder cancer cell lines in response to interferon-gamma (IFN-γ). Results: Patients with high STAT3 or p-STAT3 expression, and high platelet-to-lymphocyte ratio (PLR) (n=6) had a significantly shorter OS; in the other patients (n=25), high STAT3 or p-STAT3 expression was significantly associated with improved prognosis. IFN-γ-induced apoptosis was partially dependent on STAT3 in T24 cells but not in JMSU1 cells. Conclusion: In patients with advanced UC, STAT3 plays a key role in mediating the efficacy of pembrolizumab through apoptosis in response to IFN-γ.

Key Words:
  • Pembrolizumab
  • urothelial carcinoma
  • STAT3
  • IFN-γ
  • Received March 15, 2024.
  • Revision received March 28, 2024.
  • Accepted March 29, 2024.
  • Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Anticancer Research: 44 (5)
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STAT3 Contributes a Favorable Response to Pembrolizumab Through IFN-γ-induced Apoptosis in Urothelial Cancer
HIROTAKA FUCHIZAWA, KIYOHIRO ANDO, NORIKO MOTOI, TOSHIHIKO IIZUKA, MASAHARU INOUE, KOUKI MITANI, YUTA SANO, HISANORI TAKENOBU, MASAYUKI HARUTA, RITSUKO ONUKI, YOH MATSUOKA, TAKEHIKO KAMIJO, YUKIO KAGEYAMA
Anticancer Research May 2024, 44 (5) 1925-1930; DOI: 10.21873/anticanres.16994

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STAT3 Contributes a Favorable Response to Pembrolizumab Through IFN-γ-induced Apoptosis in Urothelial Cancer
HIROTAKA FUCHIZAWA, KIYOHIRO ANDO, NORIKO MOTOI, TOSHIHIKO IIZUKA, MASAHARU INOUE, KOUKI MITANI, YUTA SANO, HISANORI TAKENOBU, MASAYUKI HARUTA, RITSUKO ONUKI, YOH MATSUOKA, TAKEHIKO KAMIJO, YUKIO KAGEYAMA
Anticancer Research May 2024, 44 (5) 1925-1930; DOI: 10.21873/anticanres.16994
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Keywords

  • Pembrolizumab
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