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Article Open Access

Phospho‑STAT1 expression as a potential biomarker for anti‑PD‑1/anti‑PD‑L1 immunotherapy for breast cancer

  • Authors:
    • Yuko Nakayama
    • Kosaku Mimura
    • Tomoaki Tamaki
    • Kensuke Shiraishi
    • Ley‑Fang Kua
    • Vivien Koh
    • Masato Ohmori
    • Ayako Kimura
    • Shingo Inoue
    • Hirokazu Okayama
    • Yoshiyuki Suzuki
    • Tadao Nakazawa
    • Daisuke Ichikawa
    • Koji Kono
  • View Affiliations / Copyright

    Affiliations: First Department of Surgery, University of Yamanashi, Yamanashi 409‑3898, Japan, Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima, 960‑1295, Japan, Department of Radiation Oncology, Fukushima Medical University School of Medicine, Fukushima, 960‑1295, Japan, National University Cancer Institute, Singapore, National University Health System, Singapore 119228, Republic of Singapore, Department of Pathology, University of Yamanashi, Yamanashi 409‑3898, Japan
    Copyright: © Nakayama et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 4.0].
  • Pages: 2030-2038
    |
    Published online on: April 10, 2019
       https://doi.org/10.3892/ijo.2019.4779
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Abstract

In the present study, we evaluated the mechanisms of programmed death ligand 1 (PD‑L1) expression in the breast cancer microenvironment, focusing on the role of interferon‑γ (IFN‑γ), and the clinical indications for anti‑programmed cell death 1 (PD‑1) /anti‑PD‑L1 immunotherapy. We evaluated PD‑L1 expression in 4 breast cancer cell lines in the presence of 3 types of inhibitors, as well as IFN‑γ. The expression of phosphorylated signal transducer and activator of transcription 1 (p‑STAT1), one of the IFN‑γ signaling pathway molecules, was analyzed using immunohistochemistry (IHC) in relation to PD‑L1 and human leukocyte antigen (HLA) class I expression on cancer cells and tumor‑infiltrating CD8‑positive T cells in 111 patients with stage II/III breast cancer. Using The Cancer Genome Atlas (TCGA) database, the correlation of the IFN‑γ signature with PD‑L1 expression was analyzed in breast invasive carcinoma tissues. As a result, the JAK/STAT pathway via IFN‑γ was mainly involved in PD‑L1 expression in the cell lines examined. IHC analysis revealed that the PD‑L1 and HLA class I expression levels were significantly upregulated in the p‑STAT1‑positive cases. TCGA analysis indicated that the PD‑L1 expression and IFN‑γ signature exhibited a positive correlation. On the whole, these findings suggest that PD‑L1 and HLA class I are co‑expressed in p‑STAT1‑positive breast cancer cells induced by IFN‑γ secreted from tumor infiltrating immune cells, and that p‑STAT1 expression may be a potential biomarker for patient selection for immunotherapy with anti‑PD‑1/anti‑PD‑L1 monoclonal antibodies.
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Copy and paste a formatted citation
Spandidos Publications style
Nakayama Y, Mimura K, Tamaki T, Shiraishi K, Kua LF, Koh V, Ohmori M, Kimura A, Inoue S, Okayama H, Okayama H, et al: Phospho‑STAT1 expression as a potential biomarker for anti‑PD‑1/anti‑PD‑L1 immunotherapy for breast cancer. Int J Oncol 54: 2030-2038, 2019.
APA
Nakayama, Y., Mimura, K., Tamaki, T., Shiraishi, K., Kua, L., Koh, V. ... Kono, K. (2019). Phospho‑STAT1 expression as a potential biomarker for anti‑PD‑1/anti‑PD‑L1 immunotherapy for breast cancer. International Journal of Oncology, 54, 2030-2038. https://doi.org/10.3892/ijo.2019.4779
MLA
Nakayama, Y., Mimura, K., Tamaki, T., Shiraishi, K., Kua, L., Koh, V., Ohmori, M., Kimura, A., Inoue, S., Okayama, H., Suzuki, Y., Nakazawa, T., Ichikawa, D., Kono, K."Phospho‑STAT1 expression as a potential biomarker for anti‑PD‑1/anti‑PD‑L1 immunotherapy for breast cancer". International Journal of Oncology 54.6 (2019): 2030-2038.
Chicago
Nakayama, Y., Mimura, K., Tamaki, T., Shiraishi, K., Kua, L., Koh, V., Ohmori, M., Kimura, A., Inoue, S., Okayama, H., Suzuki, Y., Nakazawa, T., Ichikawa, D., Kono, K."Phospho‑STAT1 expression as a potential biomarker for anti‑PD‑1/anti‑PD‑L1 immunotherapy for breast cancer". International Journal of Oncology 54, no. 6 (2019): 2030-2038. https://doi.org/10.3892/ijo.2019.4779
Copy and paste a formatted citation
x
Spandidos Publications style
Nakayama Y, Mimura K, Tamaki T, Shiraishi K, Kua LF, Koh V, Ohmori M, Kimura A, Inoue S, Okayama H, Okayama H, et al: Phospho‑STAT1 expression as a potential biomarker for anti‑PD‑1/anti‑PD‑L1 immunotherapy for breast cancer. Int J Oncol 54: 2030-2038, 2019.
APA
Nakayama, Y., Mimura, K., Tamaki, T., Shiraishi, K., Kua, L., Koh, V. ... Kono, K. (2019). Phospho‑STAT1 expression as a potential biomarker for anti‑PD‑1/anti‑PD‑L1 immunotherapy for breast cancer. International Journal of Oncology, 54, 2030-2038. https://doi.org/10.3892/ijo.2019.4779
MLA
Nakayama, Y., Mimura, K., Tamaki, T., Shiraishi, K., Kua, L., Koh, V., Ohmori, M., Kimura, A., Inoue, S., Okayama, H., Suzuki, Y., Nakazawa, T., Ichikawa, D., Kono, K."Phospho‑STAT1 expression as a potential biomarker for anti‑PD‑1/anti‑PD‑L1 immunotherapy for breast cancer". International Journal of Oncology 54.6 (2019): 2030-2038.
Chicago
Nakayama, Y., Mimura, K., Tamaki, T., Shiraishi, K., Kua, L., Koh, V., Ohmori, M., Kimura, A., Inoue, S., Okayama, H., Suzuki, Y., Nakazawa, T., Ichikawa, D., Kono, K."Phospho‑STAT1 expression as a potential biomarker for anti‑PD‑1/anti‑PD‑L1 immunotherapy for breast cancer". International Journal of Oncology 54, no. 6 (2019): 2030-2038. https://doi.org/10.3892/ijo.2019.4779
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