Fundamental study for induction of tertiary lymphoid structure (TLS) in ovarian cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K22810
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Shizuoka Prefectural Hospital Organization (2022); Kyoto University (2020-2021)
• Principal Investigator: UKITA Masayo 地方独立行政法人静岡県立病院機構静岡県立総合病院(救急診療部、循環器病診療部、がん診療部、臨床診療部, 臨床診療部, 医長 (50725067)
• Project Period (FY): 2020-09-11 – 2023-03-31
• Keywords: 三次リンパ組織 / 腫瘍浸潤リンパ球 / 腫瘍微小環境 / 卵巣癌

Outline of Final Research Achievements

The presence of tertiary lymphoid structure(TLS) recruits various lymphocytes and enhances the infiltration of B-cell lineages and CD8+ T cells in ovarian cancer, leading to antitumor immunity. The strong interaction between humoral and cellular immunity in the antitumor response was revealed, and the possibility of TLS-mediated interactions was demonstrated. Gene expression of CXCL13, a chemokine involved in TLS formation, correlated with TLS presence and the infiltration of T cells and B cells, and was a favorable prognostic factor for high grade serous ovarian cancer patients. In a mouse ovarian cancer model, recombinant CXCL13 induced TLSs and enhanced survival by the infiltration of CD8+ T cells.This study revealed the TME can be altered by inducing CXCL13 and TLSs, which might be an important immunomodulatory method to enhance antitumor immunity.

Free Research Field

婦人科腫瘍

Academic Significance and Societal Importance of the Research Achievements

腫瘍の進行を制御し、治療への反応性を調節するという重要な役割をもつ腫瘍微小環境（TME）を標的とした治療戦略は有望なアプローチとして発展途上にある。本研究では、慢性炎症に伴ってTMEに形成される三次リンパ組織（TLS）に着目し、卵巣癌におけるTLSの臨床的意義を明らかにし、新たな治療標的としての可能性を検討した。卵巣癌における抗腫瘍反応における液性免疫との相互作用の重要性と、CXCL13やTLSの誘導はTMEを変化させうることが示された。