CXCL13-producing CD4+ T Cells Accumulate in the Early Phase of Tertiary Lymphoid Structures in Ovarian Cancer

Overview

Journal JCI Insight

Specialties Biomedical Engineering
General Medicine

Date 2022 May 13

PMID 35552285

Authors

Masayo Ukita

Junzo Hamanishi

Hiroyuki Yoshitomi

Koji Yamanoi

Shiro Takamatsu

Akihiko Ueda

Haruka Suzuki

Yuko Hosoe

Yoko Furutake

Mana Taki

Kaoru Abiko

Ken Yamaguchi

Hidekatsu Nakai

Tsukasa Baba

Noriomi Matsumura

Akihiko Yoshizawa

Hideki Ueno

Masaki Mandai

Affiliations

Soon will be listed here.

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.

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