Spontaneous high clonal expansion of Wilms’ tumor gene 1-specific cytotoxic T-lymphocytes in patients with Wilms’ tumor gene 1-expressing solid tumor

Morimoto, Soyoko; Tanaka, Yukie; Nakata, Jun; Fujiki, Fumihiro; Hasegawa, Kana; Nakajima, Hiroko; Nishida, Sumiyuki; Tsuboi, Akihiro; Hosen, Naoki; Kagawa, Naoki; Maruno, Motohiko; Myoui, Akira; Enomoto, Takayuki; Izumoto, Shuichi; Sekimoto, Mitsugu; Hashimoto, Naoya; Yoshimine, Toshiki; Kumanogoh, Atsushi; Oji, Yusuke; Oka, Yoshihiro; Sugiyama, Haruo

doi:https://doi.org/10.1007/s00262-024-03862-8

Spontaneous high clonal expansion of Wilms’ tumor gene 1-specific cytotoxic T-lymphocytes in patients with Wilms’ tumor gene 1-expressing solid tumor

Morimoto, Soyoko; Tanaka, Yukie; Nakata, Jun et al.

Cancer Immunology, Immunotherapy, 2024, 74, 15

アクセス数:45件（2025-04-04 14:30 集計）

固定URL: https://hdl.handle.net/11094/98815

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タイトル	Spontaneous high clonal expansion of Wilms’ tumor gene 1-specific cytotoxic T-lymphocytes in patients with Wilms’ tumor gene 1-expressing solid tumor
著者	NRID 1000010649023 1000010649023 researchmap permalink so-yo-ko so-yo-ko Scopus Author ID 35083938700 35083938700 ORCID 0000-0002-4939-0455 0000-0002-4939-0455 著者名 Morimoto, Soyoko
	NRID 1000010814197 1000010814197 著者名 Tanaka, Yukie
	NRID 1000090528952 1000090528952 researchmap permalink mogura mogura Scopus Author ID 37066306900 37066306900 著者名 Nakata, Jun
	NRID 1000040456926 1000040456926 researchmap permalink handai-fufujiki handai-fufujiki Scopus Author ID 6603301225 6603301225 著者名 Fujiki, Fumihiro
	NRID 1000020777370 1000020777370 researchmap permalink 111518 111518 著者名 Hasegawa, Kana
	researchmap permalink hero.nakajima hero.nakajima 著者名 Nakajima, Hiroko
	NRID 1000000403189 1000000403189 researchmap permalink sumi_nishi_12 sumi_nishi_12 Scopus Author ID 55190147500 55190147500 著者名 Nishida, Sumiyuki
	NRID 1000010372608 1000010372608 researchmap permalink atsuboi atsuboi Scopus Author ID 7005581966 7005581966 著者名 Tsuboi, Akihiro
	NRID 1000010456923 1000010456923 researchmap permalink hnaoki hnaoki Scopus Author ID 55928728700 55928728700 著者名 Hosen, Naoki
	NRID 1000050444542 1000050444542 researchmap permalink naokikagawa naokikagawa Scopus Author ID 8945727800 8945727800 著者名 Kagawa, Naoki
	NRID 1000010263287 1000010263287 著者名 Maruno, Motohiko
	NRID 1000010263261 1000010263261 researchmap permalink researchmap_myoui researchmap_myoui Scopus Author ID 7003315276 7003315276 著者名 Myoui, Akira
	NRID 1000090283754 1000090283754 ORCID 0000-0003-4538-5541 0000-0003-4538-5541 researchmap permalink Takayuki1956 Takayuki1956 著者名 Enomoto, Takayuki
	NRID 1000040324769 1000040324769 著者名 Izumoto, Shuichi
	NRID 1000010273658 1000010273658 著者名 Sekimoto, Mitsugu
	NRID 1000090315945 1000090315945 著者名 Hashimoto, Naoya
	NRID 1000000201046 1000000201046 researchmap permalink read0046477 read0046477 著者名 Yoshimine, Toshiki
	NRID 1000010294125 1000010294125 researchmap permalink read0051725 read0051725 Scopus Author ID 6602726311 6602726311 ORCID 0000-0003-4749-7117 0000-0003-4749-7117 著者名 Kumanogoh, Atsushi
	NRID 1000020294100 1000020294100 researchmap permalink OJIYusukeOsakaU1-7 OJIYusukeOsakaU1-7 Scopus Author ID 7003801749 7003801749 著者名 Oji, Yusuke
	NRID 1000020273691 1000020273691 researchmap permalink read0046463 read0046463 著者名 Oka, Yoshihiro
	NRID 1000070162906 1000070162906 researchmap permalink read0191156 read0191156 Scopus Author ID 55479602000 55479602000 著者名 Sugiyama, Haruo
キーワード等	Clonality
	Single-cell
	TCR repertoire
	WT1
	WT1126-CTLs
内容	The version of record of this article, first published in Cancer Immunology, Immunotherapy, is available online at Publisher’s website: https://doi.org/10.1007/s00262-024-03862-8.
抄録	Wilms’ tumor protein 1 (WT1)-targeted immunotherapy has been used in patients with leukemia and solid tumors. However, the spontaneous WT1-specific immune response before WT1 peptide vaccination in patients with WT1-expressing tumors (PTs) remains unclear. Therefore, we investigated whether WT1-specific cytotoxic CD8+ T-lymphocytes (CTLs) are clonally expanded in the peripheral blood outside of tumor sites. Clonal expansion of WT1126 peptide (a.a.126–134)-specific CTLs (WT1126-CTLs) was compared between seven PTs and five healthy volunteers (HVs), and their T-cell receptors (TCRs) were analyzed at the single-cell level. Overall, 433 and 351 TCR β-chains of WT1126-CTLs were detected from PTs and HVs, respectively, and complementarity-determining region 3 was sequenced for clonality analysis. The frequencies of WT1126-CTLs were higher in human leukocyte antigen (HLA)-A02:01+ PTs than in HLA-A02:01+ HVs, although the difference was not statistically significant. WT1126-CTLs of differentiated types, including memory and effector, were higher in PTs than in HVs; whereas, those of the naïve type were higher in HVs than in PTs. WT1126-CTL clonality was significantly higher in PTs than in HVs. Furthermore, the frequency of effector WT1126-CTLs positively correlated with WT1126-CTL clonality in PTs; whereas, the frequency of naïve phenotype WT1126-CTLs tended to be negatively correlated with clonality. In conclusion, these results suggest that the WT1 protein in tumor cells is highly immunogenic, thereby stimulating endogenous naïve-type WT1126-CTLs and enabling them to clonally expand and differentiate into effector-type WT1126-CTLs.
出版者	Springer Science and Business Media Deutschland GmbH
収録物名	Cancer Immunology, Immunotherapy
巻(号)	74
ページ	15
刊行年月	2024-11-07
言語	英語
ハンドルURL	https://hdl.handle.net/11094/98815
PISSN	03407004
eISSN	14320851
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1007/s00262-024-03862-8
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution 4.0 International License.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCTERMS.bibliographicCitation	Cancer Immunology, Immunotherapy. 2024, 74, p. 15
DC.title	Spontaneous high clonal expansion of Wilms’ tumor gene 1-specific cytotoxic T-lymphocytes in patients with Wilms’ tumor gene 1-expressing solid tumor
DC.creator	Morimoto, Soyoko
	Tanaka, Yukie
	Nakata, Jun
	Fujiki, Fumihiro
	Hasegawa, Kana
	Nakajima, Hiroko
	Nishida, Sumiyuki
	Tsuboi, Akihiro
	Hosen, Naoki
	Kagawa, Naoki
	Maruno, Motohiko
	Myoui, Akira
	Enomoto, Takayuki
	Izumoto, Shuichi
	Sekimoto, Mitsugu
	Hashimoto, Naoya
	Yoshimine, Toshiki
	Kumanogoh, Atsushi
	Oji, Yusuke
	Oka, Yoshihiro
	Sugiyama, Haruo
DC.publisher	Springer Science and Business Media Deutschland GmbH
DC.language' scheme='DCTERMS.RFC1766	英語
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2024-11-07
DC.identifier	https://doi.org/10.1007/s00262-024-03862-8
DC.subject	Clonality
	Single-cell
	TCR repertoire
	WT1
	WT1126-CTLs
DC.description	The version of record of this article, first published in Cancer Immunology, Immunotherapy, is available online at Publisher’s website: https://doi.org/10.1007/s00262-024-03862-8.
DCTERMS.abstract	Wilms’ tumor protein 1 (WT1)-targeted immunotherapy has been used in patients with leukemia and solid tumors. However, the spontaneous WT1-specific immune response before WT1 peptide vaccination in patients with WT1-expressing tumors (PTs) remains unclear. Therefore, we investigated whether WT1-specific cytotoxic CD8+ T-lymphocytes (CTLs) are clonally expanded in the peripheral blood outside of tumor sites. Clonal expansion of WT1126 peptide (a.a.126–134)-specific CTLs (WT1126-CTLs) was compared between seven PTs and five healthy volunteers (HVs), and their T-cell receptors (TCRs) were analyzed at the single-cell level. Overall, 433 and 351 TCR β-chains of WT1126-CTLs were detected from PTs and HVs, respectively, and complementarity-determining region 3 was sequenced for clonality analysis. The frequencies of WT1126-CTLs were higher in human leukocyte antigen (HLA)-A02:01+ PTs than in HLA-A02:01+ HVs, although the difference was not statistically significant. WT1126-CTLs of differentiated types, including memory and effector, were higher in PTs than in HVs; whereas, those of the naïve type were higher in HVs than in PTs. WT1126-CTL clonality was significantly higher in PTs than in HVs. Furthermore, the frequency of effector WT1126-CTLs positively correlated with WT1126-CTL clonality in PTs; whereas, the frequency of naïve phenotype WT1126-CTLs tended to be negatively correlated with clonality. In conclusion, these results suggest that the WT1 protein in tumor cells is highly immunogenic, thereby stimulating endogenous naïve-type WT1126-CTLs and enabling them to clonally expand and differentiate into effector-type WT1126-CTLs.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	98815
citation_title	Spontaneous high clonal expansion of Wilms’ tumor gene 1-specific cytotoxic T-lymphocytes in patients with Wilms’ tumor gene 1-expressing solid tumor
citation_author	Morimoto, Soyoko
	Tanaka, Yukie
	Nakata, Jun
	Fujiki, Fumihiro
	Hasegawa, Kana
	Nakajima, Hiroko
	Nishida, Sumiyuki
	Tsuboi, Akihiro
	Hosen, Naoki
	Kagawa, Naoki
	Maruno, Motohiko
	Myoui, Akira
	Enomoto, Takayuki
	Izumoto, Shuichi
	Sekimoto, Mitsugu
	Hashimoto, Naoya
	Yoshimine, Toshiki
	Kumanogoh, Atsushi
	Oji, Yusuke
	Oka, Yoshihiro
	Sugiyama, Haruo
citation_publisher	Springer Science and Business Media Deutschland GmbH
citation_language	英語
citation_date	2024-11-07
citation_journal_title	Cancer Immunology, Immunotherapy
citation_volume	74
citation_firstpage	15
citation_doi	https://doi.org/10.1007/s00262-024-03862-8
citation_public_url	https://hdl.handle.net/11094/98815

Spontaneous high clonal expansion of Wilms’ tumor gene 1-specific cytotoxic T-lymphocytes in patients with Wilms’ tumor gene 1-expressing solid tumor

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