Treatment of tumor-associated macrophages with PD-1 monoclonal antibodies affects vascular generation in cervical cancer via the PD-1/IRE1α/SHP2/HIF1α signaling pathway

Aging (Albany NY). 2024 Aug 28;16(17):12335-12345. doi: 10.18632/aging.206090. Epub 2024 Aug 28.

Abstract

Objective: To investigate the effect of PD-1 monoclonal antibodies in tumor-associated macrophages on angiogenesis in cervical cancer and its mechanism of action.

Methods: The effect of PD-1 monoclonal antibodies on the progression of cervical cancer was assessed using the nude mouse xenograft model and HE staining; the impact of PD-1 monoclonal antibodies on cervical cancer cell migration was evaluated using wound healing assay and Transwell assay; the effect on vascular formation in cervical cancer cells was examined using an angiogenesis assay; the impact on the expression of related proteins was tested using Western blotting.

Results: PD-1 monoclonal antibodies in tumor-associated macrophages can regulate and thus inhibit the progression of cervical cancer while promoting the expression of SHP2. Additionally, Sindilizumab inhibited the expression of tissue-type fibrinogen activator K and HIF1α through the PD-1/IRE1α/SHP2 signaling pathway, which inhibited the migration and neovascularization of cervical cancer cells.

Conclusions: This study discovered that PD-1 monoclonal antibodies in tumor-associated macrophages inhibit vascular generation inside cervical cancer by affecting the PD-1/IRE1α/SHP2/HIF1α signaling pathway, providing a new therapeutic target for the treatment of cervical cancer.

Keywords: HIF1α; IRE1α; SHP2; Sindilizumab; cervical cancer; tumor-associated macrophages.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Female
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit* / metabolism
  • Mice
  • Mice, Nude*
  • Neovascularization, Pathologic* / drug therapy
  • Neovascularization, Pathologic* / metabolism
  • Programmed Cell Death 1 Receptor* / metabolism
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11 / metabolism
  • Signal Transduction* / drug effects
  • Tumor-Associated Macrophages* / drug effects
  • Tumor-Associated Macrophages* / immunology
  • Tumor-Associated Macrophages* / metabolism
  • Uterine Cervical Neoplasms* / drug therapy
  • Uterine Cervical Neoplasms* / immunology
  • Uterine Cervical Neoplasms* / metabolism
  • Uterine Cervical Neoplasms* / pathology
  • Xenograft Model Antitumor Assays

Substances

  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Programmed Cell Death 1 Receptor
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Antibodies, Monoclonal