title: The translation elongation factor eEF2 is a novel tumor‑associated antigen overexpressed in various types of cancers.
abstract: Recent studies have shown that cancer immunotherapy could be a promising therapeutic approach for the treatment of cancer. In the present study, to identify novel tumor-associated antigens (TAAs), the proteins expressed in a panel of cancer cells were serologically screened by immunoblot analysis and the eukaryotic elongation factor 2 (eEF2) was identified as an antigen that was recognized by IgG autoantibody in sera from a group of patients with head and neck squamous cell carcinoma (HNSCC) or colon cancer. Enzyme-linked immunosorbent assay showed that serum eEF2 IgG Ab levels were significantly higher in colorectal and gastric cancer patients compared to healthy individuals. Immunohistochemistry experiments showed that the eEF2 protein was overexpressed in the majority of lung, esophageal, pancreatic, breast and prostate cancers, HNSCC, glioblastoma multiforme and non-Hodgkin's lymphoma (NHL). Knockdown of eEF2 by short hairpin RNA (shRNA) significantly inhibited the growth in four eEF2-expressing cell lines, PC14 lung cancer, PCI6 pancreatic cancer, HT1080 fibrosarcoma and A172 glioblastoma cells, but not in eEF2-undetectable MCF7 cells. Furthermore, eEF2-derived 9-mer peptides, EF786 (eEF2 786-794 aa) and EF292 (eEF2 292-300 aa), elicited cytotoxic T lymphocyte (CTL) responses in peripheral blood mononuclear cells (PBMCs) from an HLA-A*24:02- and an HLA-A*02:01-positive healthy donor, respectively, in an HLA-A-restricted manner. These results indicated that the eEF2 gene is overexpressed in the majority of several types of cancers and plays an oncogenic role in cancer cell growth. Moreover, the eEF2 gene product is immunogenic and a promising target molecule of cancer immunotherapy for several types of cancers.
authors.affiliation: Department of Cancer Stem Cell Biology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Oji
authors.affiliation: Department of Cancer Stem Cell Biology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Tatsumi
authors.affiliation: Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Fukuda
authors.affiliation: Department of Pathology, Kansai Rosai Hospital, Hyogo, Japan.
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Nakatsuka
authors.affiliation: Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Aoyagi
authors.affiliation: Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Erika
authors.initials: E
authors.lastname: Hirata
authors.affiliation: Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Isamu
authors.initials: I
authors.lastname: Nanchi
authors.affiliation: Department of Cancer Immunology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Fujiki
authors.affiliation: Department of Cancer Immunology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Nakajima
authors.affiliation: Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Syohei
authors.initials: S
authors.lastname: Shibata
authors.affiliation: Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Michiyo
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Cancer Stem Cell Biology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Hasegawa
authors.affiliation: Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Takagi
authors.affiliation: Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Ikuyo
authors.initials: I
authors.lastname: Fukuda
authors.affiliation: Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Hoshikawa
authors.affiliation: Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yui
authors.initials: Y
authors.lastname: Murakami
authors.affiliation: Department of Thoracic Oncology, Toneyama National Hospital, Osaka, Japan.
authors.forename: Masahide
authors.initials: M
authors.lastname: Mori
authors.affiliation: Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Inoue
authors.affiliation: Department of Respiratory Medicine and Allergy, Rheumatic Diseases, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Naka
authors.affiliation: Laboratory of Proteome Research, National Institute of Biomedical Innovation, Osaka, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tomonaga
authors.affiliation: Department of Internal Medicine, Takarazuka City Hospital, Hyogo, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Shimizu
authors.affiliation: Department of Internal Medicine, Nissay Hospital, Osaka, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Nakagawa
authors.affiliation: Department of Surgery, Osaka Rosai Hospital, Osaka, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Hasegawa
authors.affiliation: Department of Surgery, Osaka Rosai Hospital, Osaka, Japan.
authors.forename: Riichiro
authors.initials: R
authors.lastname: Nezu
authors.affiliation: Department of Otolaryngology and Sensory Organ Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Inohara
authors.affiliation: Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Izumoto
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Nonomura
authors.affiliation: Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Yoshimine
authors.affiliation: Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Meinoshin
authors.initials: M
authors.lastname: Okumura
authors.affiliation: Department of Pathology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Morii
authors.affiliation: Department of General Thoracic Surgery, Toneyama National Hospital, Osaka, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Maeda
authors.affiliation: Department of Cancer Immunotherapy, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Sumiyuki
authors.initials: S
authors.lastname: Nishida
authors.affiliation: Department of Biomedical Informatics, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Hosen
authors.affiliation: Department of Cancer Immunotherapy, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tsuboi
authors.affiliation: Department of Respiratory Medicine and Allergy, Rheumatic Diseases, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Oka
authors.affiliation: Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Haruo
authors.initials: H
authors.lastname: Sugiyama
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D054736:Elongation Factor 2 Kinase / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D061986:MCF-7 Cells; D009369:Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D017422:Sequence Analysis, DNA; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D007074:Immunoglobulin G; D054736:Elongation Factor 2 Kinase