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

J Ovarian Res. 2024 Dec 20;17(1):252. doi: 10.1186/s13048-024-01578-y.

Abstract

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.

Keywords: Ovarian cancer; PD-1; Regulatory T cell; TIGIT.

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes* / immunology
  • CD8-Positive T-Lymphocytes* / metabolism
  • Cell Line, Tumor
  • Disease Models, Animal*
  • Female
  • Humans
  • Mice
  • Ovarian Neoplasms* / immunology
  • Ovarian Neoplasms* / metabolism
  • Ovarian Neoplasms* / pathology
  • Ovarian Neoplasms* / therapy
  • Programmed Cell Death 1 Receptor* / metabolism
  • Receptors, Immunologic* / genetics
  • Receptors, Immunologic* / metabolism
  • T-Lymphocytes, Regulatory* / immunology
  • T-Lymphocytes, Regulatory* / metabolism

Substances

  • Receptors, Immunologic
  • T cell Ig and ITIM domain protein, mouse
  • Programmed Cell Death 1 Receptor