RT Journal Article
SR Electronic
T1 Expression of the immunoproteasome subunit β5i in non-small cell lung carcinomas
JF Journal of Clinical Pathology
JO J Clin Pathol
FD BMJ Publishing Group Ltd and Association of Clinical Pathologists
SP 300
OP 306
DO 10.1136/jclinpath-2020-206618
VO 74
IS 5
A1 Kiuchi, Takayuki
A1 Tomaru, Utano
A1 Ishizu, Akihiro
A1 Imagawa, Makoto
A1 Iwasaki, Sari
A1 Suzuki, Akira
A1 Otsuka, Noriyuki
A1 Ohhara, Yoshihito
A1 Kinoshita, Ichiro
A1 Matsuno, Yoshihiro
A1 Dosaka-Akita, Hirotoshi
A1 Kasahara, Masanori
YR 2021
UL http://jcp.bmj.com/content/74/5/300.abstract
AB 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.Data are available upon reasonable request. The data and materials used in the current study are available from the corresponding author on reasonable request.