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

  • Published online on: April 10, 2019     https://doi.org/10.3892/ijo.2019.4779
  • Pages: 2030-2038
  • Copyright: © Nakayama et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 4.0].

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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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June-2019
Volume 54 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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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