2. Academic Validation
  3. CXCL13-producing CD4+ T cells accumulate in the early phase of tertiary lymphoid structures in ovarian cancer

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

  • JCI Insight. 2022 Jun 22;7(12):e157215. doi: 10.1172/jci.insight.157215.
Masayo Ukita 1,  Junzo Hamanishi 1,  Hiroyuki Yoshitomi 2 3,  Koji Yamanoi 1,  Shiro Takamatsu 1,  Akihiko Ueda 1,  Haruka Suzuki 1,  Yuko Hosoe 1,  Yoko Furutake 1,  Mana Taki 1,  Kaoru Abiko 4,  Ken Yamaguchi 1,  Hidekatsu Nakai 5,  Tsukasa Baba 6,  Noriomi Matsumura 5,  Akihiko Yoshizawa 7,  Hideki Ueno 2 3,  Masaki Mandai 1
Affiliations

Affiliations

  • 1 Department of Gynecology and Obstetrics and.
  • 2 Department of Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
  • 3 Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto, Japan.
  • 4 Department of Obstetrics and Gynecology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan.
  • 5 Department of Obstetrics and Gynecology, Kindai University Faculty of Medicine, Osaka, Japan.
  • 6 Department of Obstetrics and Gynecology, Iwate Medical University, Iwate, Japan.
  • 7 Department of Diagnostic Pathology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
PMID: 35552285 DOI: 10.1172/jci.insight.157215
Abstract

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.

Keywords

Adaptive immunity; Cancer; Immunology; Obstetrics/gynecology; Oncology.

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