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Expression of the immunoproteasome subunit β5i in non-small cell lung carcinomas
  1. Takayuki Kiuchi1,
  2. Utano Tomaru1,
  3. Akihiro Ishizu2,
  4. Makoto Imagawa3,
  5. Sari Iwasaki3,
  6. Akira Suzuki3,
  7. Noriyuki Otsuka1,
  8. Yoshihito Ohhara4,
  9. Ichiro Kinoshita4,
  10. Yoshihiro Matsuno5,
  11. Hirotoshi Dosaka-Akita4,
  12. Masanori Kasahara1
  1. 1Department of Pathology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
  2. 2Department of Medical Laboratory Science, Faculty of Health Sciences, Hokkaido University, Sapporo, Japan
  3. 3Department of Diagnostic Pathology, KKR Sapporo Medical Center, Sapporo, Hokkaido, Japan
  4. 4Department of Medical Oncology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
  5. 5Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan
  1. Correspondence to Dr Utano Tomaru, Department of Pathology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan; tomaruu{at}med.hokudai.ac.jp

Abstract

Aim The immunoproteasome is a specific proteasome isoform whose proteolytic activity enhances the generation of antigenic peptides to be presented by major histocompatibility complex class I molecules to CD8+ T cells. Physiologically, it is expressed abundantly in immune cells and is induced in somatic cells by cytokines, especially interferon-γ. Recently, variable expression of immunoproteasomes has been demonstrated in different types of cancers. However, the clinical significance of immunoproteasome expression in malignant tumours is poorly understood. In this study, we performed clinicopathological evaluation of immunoproteasome subunit β5i in non-small cell lung carcinomas (NSCLCs).

Methods Tumour tissues were collected from 155 patients with NSCLCs, and immunohistochemical analysis for β5i was performed in relation to the prognosis of patients.

Results High expression of β5i was found in about 20% of all NSCLCs and was found significantly more frequently (40%) in the adenocarcinoma subset. High expression of β5i was associated with a better 5-year relative survival rate in patients with pStage I to II adenocarcinoma and was also a significant and independent favourable prognostic factor in adenocarcinoma patients. In addition, when we performed in vitro analysis using NSCLC cell lines, combined treatment with the immunoproteasome-specific inhibitor ONX0914 and the proteasome inhibitor MG132 enhanced cell death in β5i-expressing NSCLC cell lines.

Conclusion The expression of immunoproteasome can be explored as both a prognostic factor and a potential therapeutic target in NSCLCs. Since immunoproteasomes have crucial role in the antigen presentation, further studies may help to provide essential knowledge for therapeutic strategies in anticancer immunotherapy.

  • lung neoplasms
  • immunohistochemistry
  • pathology, surgical
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Footnotes

  • Handling editor Dhirendra Govender.

  • Contributors TK and UT designed the study, analysed the data and wrote the manuscript. AI, MI, SI and AS evaluated immunological staining and performed in vitro experiments. NO, YO and IK analysed the clinical data. YM analysed the data, supervised the research design and edited the manuscript. HDA and MK reviewed and supervised the manuscript. All authors gave final approval for publication.

  • Funding This work was supported in part by Grants-in-Aid for Scientific Research from The Ministry of Education, Culture, Sports, Science and Technology of Japan (18H02629) and by the Smoking Research Foundation (2018G008).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval This study was approved by the Medical Ethics Committee of Hokkaido University Hospital (Approval number 015–0118). The need for written informed consent was waived.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request. The data and materials used in the current study are available from the corresponding author on reasonable request.

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