PMID- 29632734 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210112 IS - 2162-4011 (Print) IS - 2162-402X (Electronic) IS - 2162-4011 (Linking) VI - 7 IP - 4 DP - 2018 TI - Bladder cancer-associated cancer-testis antigen-derived long peptides encompassing both CTL and promiscuous HLA class II-restricted Th cell epitopes induced CD4(+) T cells expressing converged T-cell receptor genes in vitro. PG - e1415687 LID - 10.1080/2162402X.2017.1415687 [doi] LID - e1415687 AB - DEP domain containing 1 (DEPDC1) and M-phase phosphoprotein 1 (MPHOSPH1) are human cancer testis antigens that are frequently overexpressed in urinary bladder cancer. In a phase I/II clinical trial, a DEPDC1- and MPHOSPH1-derived short peptide vaccine demonstrated promising efficacy in preventing bladder cancer recurrence. Here, we aimed to identify long peptides (LPs) derived from DEPDC1 and MPHOSPH1 that induced both T-helper (Th) cells and tumor-reactive cytotoxic T lymphocytes (CTLs). Stimulation of peripheral blood mononuclear cells (PBMCs) from healthy donors with the synthetic DEPDC1- and MPHOSPH1-LPs predicted to bind to promiscuous human leukocyte antigen (HLA) class II molecules by a computer algorithm induced specific CD4(+) T cells as revealed by interferon-gamma enzyme-linked immunospot assays. Three of six LPs encompassed HLA-A2- or -A24-restricted CTL epitopes or both, and all six LPs stimulated DEPDC1- or MPHOSPH1-specific Th cells restricted by promiscuous and frequently observed HLA class II molecules in the Japanese population. Some LPs are naturally processed from the proteins in DCs, and the capacity of these LPs to cross-prime CTLs was confirmed in vivo using HLA-A2 or -A24 transgenic mice. The LP-specific and HLA class II-restricted T-cell responses were also observed in PBMCs from patients with bladder cancer. Repeated stimulation of PBMCs with DEPDC1-LPs and MPHOSPH1-LPs yielded clonal Th cells expressing specific T-cell receptor (TCR)-alpha and beta genes. These DEPDC1- or MPHOSPH1-derived LPs may have applications in immunotherapy in patients with bladder cancer, and the TCR genes identified may be useful for monitoring of Th cells specific to LPs in vivo. FAU - Tsuruta, Miki AU - Tsuruta M AD - Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Honjo, Chuo-ku, Kumamoto, Japan. AD - Department of Oral and Maxillofacial Surgery, Graduate School of Medical Sciences, Kumamoto University, Honjo, Chuo-ku, Kumamoto, Japan. FAU - Ueda, Shohei AU - Ueda S AD - Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Honjo, Chuo-ku, Kumamoto, Japan. AD - Department of Urology, Graduate School of Medical Sciences, Kyushu University, Maidashi, Higashi-ku, Fukuoka, Japan. FAU - Yew, Poh Yin AU - Yew PY AD - Tumor Immunoanalysis Department, OncoTherapy Science, Inc., Sakado, Takatsu-ku, Kawasaki, Kanagawa, Japan. FAU - Fukuda, Isao AU - Fukuda I AD - Tumor Immunoanalysis Department, OncoTherapy Science, Inc., Sakado, Takatsu-ku, Kawasaki, Kanagawa, Japan. FAU - Yoshimura, Sachiko AU - Yoshimura S AD - Tumor Immunoanalysis Department, OncoTherapy Science, Inc., Sakado, Takatsu-ku, Kawasaki, Kanagawa, Japan. FAU - Kishi, Hiroyuki AU - Kishi H AD - Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences (Medicine), University of Toyama, Sugitani, Toyama, Toyama, Japan. FAU - Hamana, Hiroshi AU - Hamana H AD - Department of Innovative Cancer Immunotherapy, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama, Toyama, Japan. FAU - Hirayama, Masatoshi AU - Hirayama M AD - Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Honjo, Chuo-ku, Kumamoto, Japan. AD - Department of Oral and Maxillofacial Surgery, Graduate School of Medical Sciences, Kumamoto University, Honjo, Chuo-ku, Kumamoto, Japan. FAU - Yatsuda, Junji AU - Yatsuda J AD - Department of Urology, Graduate School of Medical Sciences, Kumamoto University, Honjo, Chuo-ku, Kumamoto, Japan. FAU - Irie, Atsushi AU - Irie A AD - Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Honjo, Chuo-ku, Kumamoto, Japan. FAU - Senju, Satoru AU - Senju S AD - Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Honjo, Chuo-ku, Kumamoto, Japan. FAU - Yuba, Eiji AU - Yuba E AD - Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, Gakuen-cho, Naka-ku, Sakai, Osaka, Japan. FAU - Kamba, Tomomi AU - Kamba T AD - Department of Urology, Graduate School of Medical Sciences, Kumamoto University, Honjo, Chuo-ku, Kumamoto, Japan. FAU - Eto, Masatoshi AU - Eto M AD - Department of Urology, Graduate School of Medical Sciences, Kyushu University, Maidashi, Higashi-ku, Fukuoka, Japan. AD - Department of Urology, Graduate School of Medical Sciences, Kumamoto University, Honjo, Chuo-ku, Kumamoto, Japan. FAU - Nakayama, Hideki AU - Nakayama H AD - Department of Oral and Maxillofacial Surgery, Graduate School of Medical Sciences, Kumamoto University, Honjo, Chuo-ku, Kumamoto, Japan. FAU - Nishimura, Yasuharu AU - Nishimura Y AD - Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Honjo, Chuo-ku, Kumamoto, Japan. AD - Nishimura Project Laboratory, Center for Resource Development and Analysis, Kumamoto University, Honjo, Chuo-ku, Kumamoto, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180105 PL - United States TA - Oncoimmunology JT - Oncoimmunology JID - 101570526 PMC - PMC5889196 OTO - NOTNLM OT - DEP domain containing 1 OT - M-phase phosphoprotein 1 OT - T-cell receptor OT - bladder cancer OT - cancer immunotherapy OT - cancer-testis antigen OT - cross presentation OT - helper T-cell epitope OT - tumor immunity EDAT- 2018/04/11 06:00 MHDA- 2018/04/11 06:01 PMCR- 2019/01/05 CRDT- 2018/04/11 06:00 PHST- 2017/10/11 00:00 [received] PHST- 2017/12/02 00:00 [revised] PHST- 2017/12/04 00:00 [accepted] PHST- 2018/04/11 06:00 [entrez] PHST- 2018/04/11 06:00 [pubmed] PHST- 2018/04/11 06:01 [medline] PHST- 2019/01/05 00:00 [pmc-release] AID - 1415687 [pii] AID - 10.1080/2162402X.2017.1415687 [doi] PST - epublish SO - Oncoimmunology. 2018 Jan 5;7(4):e1415687. doi: 10.1080/2162402X.2017.1415687. eCollection 2018.