PMID- 31081058
OWN - NLM
STAT- MEDLINE
DCOM- 20190830
LR  - 20200225
IS  - 1791-2423 (Electronic)
IS  - 1019-6439 (Print)
IS  - 1019-6439 (Linking)
VI  - 54
IP  - 6
DP  - 2019 Jun
TI  - Phospho‑STAT1 expression as a potential biomarker for anti‑PD‑1/anti‑PD‑L1 
      immunotherapy for breast cancer.
PG  - 2030-2038
LID - 10.3892/ijo.2019.4779 [doi]
AB  - 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‑gamma (IFN‑gamma), 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‑gamma. The expression of phosphorylated signal transducer and activator of 
      transcription 1 (p‑STAT1), one of the IFN‑gamma 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‑gamma signature with 
      PD‑L1 expression was analyzed in breast invasive carcinoma tissues. As a result, 
      the JAK/STAT pathway via IFN‑gamma 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‑gamma 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‑gamma 
      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.
FAU - Nakayama, Yuko
AU  - Nakayama Y
AD  - First Department of Surgery, University of Yamanashi, Yamanashi 409‑3898, Japan.
FAU - Mimura, Kosaku
AU  - Mimura K
AD  - Department of Gastrointestinal Tract Surgery, Fukushima Medical University School 
      of Medicine, Fukushima, 960‑1295, Japan.
FAU - Tamaki, Tomoaki
AU  - Tamaki T
AD  - Department of Radiation Oncology, Fukushima Medical University School of 
      Medicine, Fukushima, 960‑1295, Japan.
FAU - Shiraishi, Kensuke
AU  - Shiraishi K
AD  - First Department of Surgery, University of Yamanashi, Yamanashi 409‑3898, Japan.
FAU - Kua, Ley-Fang
AU  - Kua LF
AD  - National University Cancer Institute, Singapore, National University Health 
      System, Singapore 119228, Republic of Singapore.
FAU - Koh, Vivien
AU  - Koh V
AD  - National University Cancer Institute, Singapore, National University Health 
      System, Singapore 119228, Republic of Singapore.
FAU - Ohmori, Masato
AU  - Ohmori M
AD  - First Department of Surgery, University of Yamanashi, Yamanashi 409‑3898, Japan.
FAU - Kimura, Ayako
AU  - Kimura A
AD  - First Department of Surgery, University of Yamanashi, Yamanashi 409‑3898, Japan.
FAU - Inoue, Shingo
AU  - Inoue S
AD  - First Department of Surgery, University of Yamanashi, Yamanashi 409‑3898, Japan.
FAU - Okayama, Hirokazu
AU  - Okayama H
AD  - Department of Gastrointestinal Tract Surgery, Fukushima Medical University School 
      of Medicine, Fukushima, 960‑1295, Japan.
FAU - Suzuki, Yoshiyuki
AU  - Suzuki Y
AD  - Department of Radiation Oncology, Fukushima Medical University School of 
      Medicine, Fukushima, 960‑1295, Japan.
FAU - Nakazawa, Tadao
AU  - Nakazawa T
AD  - Department of Pathology, University of Yamanashi, Yamanashi 409‑3898, Japan.
FAU - Ichikawa, Daisuke
AU  - Ichikawa D
AD  - First Department of Surgery, University of Yamanashi, Yamanashi 409‑3898, Japan.
FAU - Kono, Koji
AU  - Kono K
AD  - Department of Gastrointestinal Tract Surgery, Fukushima Medical University School 
      of Medicine, Fukushima, 960‑1295, Japan.
LA  - eng
PT  - Journal Article
DEP - 20190410
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (B7-H1 Antigen)
RN  - 0 (CD274 protein, human)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (IFNG protein, human)
RN  - 0 (STAT1 Transcription Factor)
RN  - 0 (STAT1 protein, human)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - B7-H1 Antigen/*genetics/*metabolism
MH  - Breast Neoplasms/drug therapy/genetics/metabolism/*pathology
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Cell Line, Tumor
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Histocompatibility Antigens Class I/metabolism
MH  - Humans
MH  - Immunotherapy
MH  - Interferon-gamma/metabolism
MH  - Lymphocytes, Tumor-Infiltrating/immunology
MH  - MCF-7 Cells
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Phosphorylation
MH  - STAT1 Transcription Factor/*metabolism
MH  - Tumor Microenvironment
MH  - *Up-Regulation
PMC - PMC6521934
EDAT- 2019/05/14 06:00
MHDA- 2019/08/31 06:00
PMCR- 2019/04/10
CRDT- 2019/05/14 06:00
PHST- 2018/10/05 00:00 [received]
PHST- 2019/02/06 00:00 [accepted]
PHST- 2019/05/14 06:00 [entrez]
PHST- 2019/05/14 06:00 [pubmed]
PHST- 2019/08/31 06:00 [medline]
PHST- 2019/04/10 00:00 [pmc-release]
AID - ijo-54-06-2030 [pii]
AID - 10.3892/ijo.2019.4779 [doi]
PST - ppublish
SO  - Int J Oncol. 2019 Jun;54(6):2030-2038. doi: 10.3892/ijo.2019.4779. Epub 2019 Apr 
      10.