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Title: CXCL13-producing CD4⁺ T cells accumulate in the early phase of tertiary lymphoid structures in ovarian cancer
Authors: Ukita, Masayo
Hamanishi, Junzo
Yoshitomi, Hiroyuki
Yamanoi, Koji
Takamatsu, Shiro
Ueda, Akihiko
Suzuki, Haruka
Hosoe, Yuko
Furutake, Yoko
Taki, Mana
Abiko, Kaoru
Yamaguchi, Ken
Nakai, Hidekatsu
Baba, Tsukasa
Matsumura, Noriomi
Yoshizawa, Akihiko
Ueno, Hideki
Mandai, Masaki
Author's alias: 浮田, 真沙世
濵西, 潤三
吉富, 啓之
山ノ井, 康二
高松, 士朗
植田, 彰彦
鈴木, 悠
細江, 裕子
古武, 陽子
滝, 真奈
安彦, 郁
山口, 建
中井, 英勝
馬場, 長
松村, 謙臣
吉澤, 明彦
上野, 英樹
万代, 昌紀
Keywords: Immunology
Issue Date: 22-Jun-2022
Publisher: American Society for Clinical Investigation
Journal title: JCI Insight
Volume: 7
Issue: 12
Thesis number: e157215
Abstract: Tertiary lymphoid structures (TLSs) are transient ectopic lymphoid aggregates whose formation might be caused by chronic inflammation states, such as cancer. However, how TLSs are induced in the tumor microenvironment (TME) and how they affect patient survival are not well understood. We investigated TLS distribution in relation to tumor infiltrating lymphocytes (TILs) and related gene expression in high grade serous ovarian cancer (HGSC) specimens. CXCL13 gene expression correlated with TLS presence and the infiltration of T cells and B cells, and was a favorable prognostic factor for HGSC patients. Coexistence of CD8⁺ T cells and B-cell lineages in the TME significantly improved the prognosis of HGSC and was correlated with the presence of TLSs. CXCL13 expression was predominantly coincident with CD4⁺ T cells in TLSs and CD8⁺ T cells in TILs, and shifted from CD4⁺ T cells to CD21⁺ follicular dendritic cells as TLS matured. In a mouse ovarian cancer model, recombinant CXCL13 induced TLSs and enhanced survival by the infiltration of CD8⁺ T cells. These results suggest that TLS formation was associated with CXCL13-producing CD4⁺ T cells and that TLSs facilitated the coordinated antitumor response of cellular and humoral immunity in ovarian cancer.
Description: 卵巣がんにおける新たな免疫の仕組みを発見 --三次リンパ様構造の形成メカニズムと予後への影響を解明--. 京都大学プレスリリース. 2022-08-05.
Rights: © 2022 Ukita et al.
This work is licensed under the Creative Commons Attribution 4.0 International License.
DOI(Published Version): 10.1172/jci.insight.157215
PubMed ID: 35552285
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