Cisplatin resistance driver claspin is a target for immunotherapy in urothelial carcinoma

被引:2
作者
Yamada, Shuhei [1 ,2 ]
Miyata, Haruka [2 ]
Isono, Makoto [3 ]
Hori, Kanta [1 ,2 ]
Yanagawa, Junko [1 ]
Murai, Aiko [1 ]
Minowa, Tomoyuki [1 ,4 ]
Mizue, Yuka [1 ]
Sasaki, Kenta [1 ,5 ]
Murata, Kenji [1 ]
Tokita, Serina [1 ]
Nakatsugawa, Munehide [6 ]
Iwabuchi, Sadahiro [7 ]
Hashimoto, Shinichi [7 ]
Kubo, Terufumi [1 ]
Kanaseki, Takayuki [1 ]
Tsukahara, Tomohide [1 ]
Abe, Takashige [2 ]
Shinohara, Nobuo [2 ]
Hirohashi, Yoshihiko [1 ]
Torigoe, Toshihiko [1 ]
机构
[1] Sapporo Med Univ, Dept Pathol, Sch Med, South 1 West 17,Chuo Ku, Sapporo, Hokkaido 0608556, Japan
[2] Hokkaido Univ, Dept Renal & Genitourinary Surg, Grad Sch Med, Sapporo, Hokkaido 0608648, Japan
[3] Abiko Toho Hosp, Dept Urol, Abiko 2701166, Japan
[4] Sapporo Med Univ, Dept Dermatol, Sch Med, Sapporo, Hokkaido 0608556, Japan
[5] Asahikawa Med Univ, Dept Dermatol, Sch Med, Asahikawa, Hokkaido 0788510, Japan
[6] Tokyo Med Univ, Dept Pathol, Hachioji Med Ctr, Hachioji, Tokyo 1930998, Japan
[7] Wakayama Med Univ, Inst Adv Med, Dept Mol Pathophysiol, Wakayama 6418509, Japan
基金
日本科学技术振兴机构; 日本学术振兴会;
关键词
Urothelial carcinoma; Claspin; Cisplatin resistance; Immunotherapy; CD8(+) T-CELLS; STEM-CELL; ANTIGEN; PLACEBO;
D O I
10.1007/s00262-023-03388-5
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:2057 / 2065
页数:9
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