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

• Published in: Journal of ovarian research Vol. 17; no. 1; pp. 252 - 10
• Main Authors: Chen, Fengzhen, Xu, Yanying, Liu, Xiangyu, Dong, Na, Tian, Lei
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 20.12.2024; BMC
• Subjects: Analysis; Animals; Antibodies; Cancer; Care and treatment; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Line, Tumor; Disease Models, Animal; Female; Growth; Health aspects; Humans; Immunotherapy; Mice; Ovarian cancer; Ovarian Neoplasms - immunology; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Ovarian Neoplasms - therapy; PD-1; Programmed Cell Death 1 Receptor - metabolism; Receptors, Immunologic - genetics; Receptors, Immunologic - metabolism; Regulatory T cell; T cells; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; TIGIT; Viral antibodies; TIGIT; PD-1; Regulatory T cell; Ovarian cancer
• DOI: 10.1186/s13048-024-01578-y
• ISSN: 1757-2215

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.