TIGIT+ CD4+ regulatory T cells enhance PD-1 expression on CD8+ T cells and promote tumor growth in a murine ovarian cancer model

被引：0

作者：

Fengzhen Chen ^{[1
]}

Yanying Xu ^{[1
]}

Xiangyu Liu ^{[2
]}

Na Dong ^{[1
]}

Lei Tian ^{[3
]}

机构：

[1] Department of Gynecology, The Second Hospital of Tianjin Medical University, Tianjin

[2] Tianjin Medical University Cancer Institute and Hospital, Tianjin

[3] Department of Gynecology and Obstetrics, The Affiliated Hospital of Nankai University, Tianjin No. 4 Hospital, Tianjin

来源：

Journal of Ovarian Research | / 17卷 / 1期

关键词：

Ovarian cancer; PD-1; Regulatory T cell; TIGIT;

D O I：

10.1186/s13048-024-01578-y

中图分类号：

学科分类号：

摘要：

Immune checkpoint-based immunotherapy has shown limited efficacy in the treatment of ovarian cancer. In recent years, the emergence of immune checkpoint co-targeting therapies, led by the combination targeting of TIGIT and FAK, has shown promise in ovarian cancer treatment. Our preliminary research indicates that TIGIT is predominantly expressed in regulatory T cells during ovarian cancer. However, the therapeutic impact of TIGIT targeting based on regulatory T cells in ovarian cancer remains to be elucidated. We utilized ID8 cells to establish a mouse model of ovarian cancer. Through flow cytometry and co-culture methods, we validated the relationship between the functionality of regulatory T cells and tumor masses, and confirmed the crucial role of TIGIT in immune suppression in ovarian cancer. Furthermore, using Foxp3-diphtheria toxin receptor (DTR) mice, we substantiated that the combined TIGIT antibody treatment, based on targeting regulatory T cells, effectively slowed down the progression of ovarian cancer. Taken together, our results have demonstrated that dual targeting of regulatory T cells and TIGIT effectively retards tumor growth, laying the groundwork for the clinical application of immune checkpoint combination therapies. Future research in ovarian cancer immunotherapy is leaning towards a strategy that combines multiple targets, and specific cell-type immunotherapies. © The Author(s) 2024.

引用

共 34 条

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