CXCL13-producing CD4+T cells accumulate in the early phase of tertiary lymphoid structures in ovarian cancer

被引：123

作者：

Ukita, Masayo ^{[1
]}

Hamanishi, Junzo ^{[1
]}

Yoshitomi, Hiroyuki ^{[2
,3
]}

Yamanoi, Koji ^{[1
]}

Takamatsu, Shiro ^{[1
]}

Ueda, Akihiko ^{[1
]}

Suzuki, Haruka ^{[1
]}

Hosoe, Yuko ^{[1
]}

Furutake, Yoko ^{[1
]}

Taki, Mana ^{[1
]}

Abiko, Kaoru ^{[4
]}

Yamaguchi, Ken ^{[1
]}

Nakai, Hidekatsu ^{[5
]}

Baba, Tsukasa ^{[6
]}

Matsumura, Noriomi ^{[5
]}

Yoshizawa, Akihiko ^{[7
]}

Ueno, Hideki ^{[2
,3
]}

Mandai, Masaki ^{[1
]}

机构：

[1] Kyoto Univ, Grad Sch Med, Dept Gynecol & Obstet, Kyoto, Japan

[2] Kyoto Univ, Grad Sch Med, Dept Immunol, Kyoto, Japan

[3] Kyoto Univ, Inst Adv Study Human Biol ASHBi, Kyoto, Japan

[4] Natl Hosp Org, Dept Obstet & Gynecol, Kyoto Med Ctr, Kyoto, Japan

[5] Kindai Univ, Dept Obstet & Gynecol, Fac Med, Osaka, Japan

[6] Iwate Med Univ, Dept Obstet & Gynecol, Kyoto, Iwate, Japan

[7] Kyoto Univ, Dept Diagnost Pathol, Grad Sch Med, Kyoto, Japan

来源：

JCI INSIGHT | 2022年 / 7卷 / 12期

关键词：

FOLLICULAR DENDRITIC CELLS; INFILTRATING PLASMA-CELLS; B-CELLS; T-CELLS; PROGNOSTIC RELEVANCE; GERMINAL-CENTERS; GROWTH-FACTOR; IMMUNOTHERAPY; CHEMOKINE; FOLLICLES;

D O I：

10.1172/jci.insight.157215

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Tertiary lymphoid structures (TLS) are transient ectopic lymphoid aggregates whose formation might be caused by chronic inflammation states, such as cancer. However, how TLS 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 it was a favorable prognostic factor for patients with HGSC. 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 TLS. CXCL13 expression was predominantly coincident with CD4+ T cells in TLS and CD8+ T cells in TILs, and it shifted from CD4+ T cells to CD21+ follicular DCs as TLS matured. In a mouse ovarian cancer model, recombinant CXCL13 induced TLS 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 TLS facilitated the coordinated antitumor response of cellular and humoral immunity in ovarian cancer.

引用

页数：16

共 51 条

[1] PD-L1 on Tumor Cells Is Induced in Ascites and Promotes Peritoneal Dissemination of Ovarian Cancer through CTL Dysfunction [J].