PMID- 36795123 OWN - NLM STAT- MEDLINE DCOM- 20230615 LR - 20240426 IS - 1432-0851 (Electronic) IS - 0340-7004 (Print) IS - 0340-7004 (Linking) VI - 72 IP - 7 DP - 2023 Jul TI - Cisplatin resistance driver claspin is a target for immunotherapy in urothelial carcinoma. PG - 2057-2065 LID - 10.1007/s00262-023-03388-5 [doi] AB - Bladder cancer is a major and fatal urological disease. Cisplatin is a key drug for the treatment of bladder cancer, especially in muscle-invasive cases. In most cases of bladder cancer, cisplatin is effective; however, resistance to cisplatin has a significant negative impact on prognosis. Thus, a treatment strategy for cisplatin-resistant bladder cancer is essential to improve the prognosis. In this study, we established a cisplatin-resistant (CR) bladder cancer cell line using an urothelial carcinoma cell lines (UM-UC-3 and J82). We screened for potential targets in CR cells and found that claspin (CLSPN) was overexpressed. CLSPN mRNA knockdown revealed that CLSPN had a role in cisplatin resistance in CR cells. In our previous study, we identified human leukocyte antigen (HLA)-A*02:01-restricted CLSPN peptide by HLA ligandome analysis. Thus, we generated a CLSPN peptide-specific cytotoxic T lymphocyte clone that recognized CR cells at a higher level than wild-type UM-UC-3 cells. These findings indicate that CLSPN is a driver of cisplatin resistance and CLSPN peptide-specific immunotherapy may be effective for cisplatin-resistant cases. CI - (c) 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Yamada, Shuhei AU - Yamada S AD - Departments of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, Hokkaido, 060-8556, Japan. AD - Department of Renal and Genitourinary Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, 060-8648, Japan. FAU - Miyata, Haruka AU - Miyata H AD - Department of Renal and Genitourinary Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, 060-8648, Japan. FAU - Isono, Makoto AU - Isono M AD - Department of Urology, Abiko Toho Hospital, Abiko, 270-1166, Japan. FAU - Hori, Kanta AU - Hori K AD - Departments of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, Hokkaido, 060-8556, Japan. AD - Department of Renal and Genitourinary Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, 060-8648, Japan. FAU - Yanagawa, Junko AU - Yanagawa J AD - Departments of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, Hokkaido, 060-8556, Japan. FAU - Murai, Aiko AU - Murai A AD - Departments of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, Hokkaido, 060-8556, Japan. FAU - Minowa, Tomoyuki AU - Minowa T AD - Departments of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, Hokkaido, 060-8556, Japan. AD - Departments of Dermatology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, 060-8556, Japan. FAU - Mizue, Yuka AU - Mizue Y AD - Departments of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, Hokkaido, 060-8556, Japan. FAU - Sasaki, Kenta AU - Sasaki K AD - Departments of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, Hokkaido, 060-8556, Japan. AD - Department of Dermatology, Asahikawa Medical University School of Medicine, Asahikawa, Hokkaido, 078-8510, Japan. FAU - Murata, Kenji AU - Murata K AD - Departments of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, Hokkaido, 060-8556, Japan. FAU - Tokita, Serina AU - Tokita S AD - Departments of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, Hokkaido, 060-8556, Japan. FAU - Nakatsugawa, Munehide AU - Nakatsugawa M AD - Department of Pathology, Tokyo Medical University Hachioji Medical Center, Hachioji, Tokyo, 193-0998, Japan. FAU - Iwabuchi, Sadahiro AU - Iwabuchi S AD - Department of Molecular Pathophysiology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Wakayama, 641-8509, Japan. FAU - Hashimoto, Shinichi AU - Hashimoto S AD - Department of Molecular Pathophysiology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Wakayama, 641-8509, Japan. FAU - Kubo, Terufumi AU - Kubo T AD - Departments of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, Hokkaido, 060-8556, Japan. FAU - Kanaseki, Takayuki AU - Kanaseki T AD - Departments of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, Hokkaido, 060-8556, Japan. FAU - Tsukahara, Tomohide AU - Tsukahara T AD - Departments of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, Hokkaido, 060-8556, Japan. FAU - Abe, Takashige AU - Abe T AD - Department of Renal and Genitourinary Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, 060-8648, Japan. FAU - Shinohara, Nobuo AU - Shinohara N AD - Department of Renal and Genitourinary Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, 060-8648, Japan. FAU - Hirohashi, Yoshihiko AU - Hirohashi Y AD - Departments of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, Hokkaido, 060-8556, Japan. hirohash@sapmed.ac.jp. FAU - Torigoe, Toshihiko AU - Torigoe T AD - Departments of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, Hokkaido, 060-8556, Japan. torigoe@sapmed.ac.jp. LA - eng GR - JPMJCR15G3/Japan Science and Technology Agency/ GR - 20cm0106352h0002/Japan Agency for Medical Research and Development/ GR - 22ama221317h0001/Japan Agency for Medical Research and Development/ GR - 16770510/Japan Agency for Medical Research and Development/ GR - 20H03460/Japan Society for the Promotion of Science/ GR - 17H01540/Japan Society for the Promotion of Science/ PT - Journal Article DEP - 20230216 PL - Germany TA - Cancer Immunol Immunother JT - Cancer immunology, immunotherapy : CII JID - 8605732 RN - Q20Q21Q62J (Cisplatin) RN - 0 (CLSPN protein, human) RN - 0 (Adaptor Proteins, Signal Transducing) SB - IM MH - Humans MH - Cell Line, Tumor MH - *Urinary Bladder Neoplasms/drug therapy/immunology/metabolism/therapy MH - Cisplatin/therapeutic use MH - *Drug Resistance, Neoplasm MH - Immunotherapy MH - *Adaptor Proteins, Signal Transducing/metabolism MH - Up-Regulation MH - T-Lymphocytes, Cytotoxic/cytology MH - Neoplastic Stem Cells/drug effects PMC - PMC10992486 OTO - NOTNLM OT - Cisplatin resistance OT - Claspin OT - Immunotherapy OT - Urothelial carcinoma COIS- The authors have no financial conflicts of interest to disclose. EDAT- 2023/02/17 06:00 MHDA- 2023/06/15 06:42 PMCR- 2023/02/16 CRDT- 2023/02/16 11:04 PHST- 2022/11/10 00:00 [received] PHST- 2023/01/25 00:00 [accepted] PHST- 2023/06/15 06:42 [medline] PHST- 2023/02/17 06:00 [pubmed] PHST- 2023/02/16 11:04 [entrez] PHST- 2023/02/16 00:00 [pmc-release] AID - 10.1007/s00262-023-03388-5 [pii] AID - 3388 [pii] AID - 10.1007/s00262-023-03388-5 [doi] PST - ppublish SO - Cancer Immunol Immunother. 2023 Jul;72(7):2057-2065. doi: 10.1007/s00262-023-03388-5. Epub 2023 Feb 16.