Details

Autor(en) / Beteiligte

• Zhang, Hongyu
• Jiang, Rong
• Zhou, Jinhua
• Wang, Juan
• Xu, Yuejuan
• Zhang, He
• Gu, Yanzheng
• Fu, Fengqing
• Shen, Yu
• Zhang, Guangbo
• Feng, Lanlan
• Zhang, Xueguang
• Chen, Youguo
• Shen, Fangrong

Titel

CTL Attenuation Regulated by PS1 in Cancer-Associated Fibroblast

Ist Teil von

• Frontiers in immunology, 2020-06, Vol.11, p.999-999

Ort / Verlag

Switzerland: Frontiers Media S.A

Erscheinungsjahr

2020

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Cancer-associated fibroblasts (CAFs) were associated with tumor progression in the tumor microenvironment (TME). However, their immunosuppressive roles in protecting cancer cells from the attack by cytotoxic T lymphocytes (CTLs) are not fully clear. In this study, we investigated whether and how CAFs regulate tumor-infiltrating lymphocytes as well as their role in tumor immunosuppression. Eighty-three cases of ovarian cancer and 10 controls were analyzed for CAFs and CD8+ tumor-infiltrating lymphocytes by gene array and immunohistochemistry. We evaluated presenilin 1 (PS1) expression in CAFs, CTL penetration, tumor burden, dendritic cell function, and migration of tumor-infiltrating lymphocytes and their function and after silencing PS1. In addition, the pathway via which PS1 affects the TME was also evaluated. PS1 was highly expressed in CAFs, and its silencing significantly promoted CD8+ CTL proliferation and penetration in multiple ovarian models ( < 0.05), resulting in tumor regression and growth inhibition. Interleukin (IL)-1β was identified as a major immune inhibitor in the TME, and it was significantly decreased after PS1 silencing ( < 0.05), which was regulated by the WNT/β-catenin pathway. It was also showed that high expression of IL-1β in CAFs inhibits CTL penetration significantly ( < 0.05). Highly expressed PS1 in CAFs plays a crucial role in regulating tumor-infiltrating lymphocyte populations in the TME via the WNT/β-catenin pathway. Targeting PS1 may retrieve functional CTLs in the TME and improve the efficacy of current immunotherapies.