Targeting pro-inflammatory T cells as a novel therapeutic approach to potentially resolve atherosclerosis in humans

Area of Science:

• Cardiovascular Research
• Immunology
• Oncology

Background:

• Atherosclerosis (AS) is a major cause of cardiovascular disease, driven by lipid accumulation and inflammation.
• Current treatments focus on lipid reduction, but residual inflammatory risks persist, highlighting the need for novel therapeutic strategies.
• The role of adaptive immunity in AS progression is not fully understood.

Purpose of the Study:

• To investigate the potential of T cell-targeting immunotherapy in resolving atherosclerosis.
• To explore the mechanism by which anti-programmed cell death protein 1 (PD-1) monoclonal antibodies (mAbs) affect AS plaque size.
• To determine the role of Fc-binding capability in the efficacy of anti-PD-1 mAbs for AS.

Main Methods:

• Retrospective and prospective cohort studies on tumor patients with AS plaques.
• Multi-omics single-cell analyses to characterize AS plaque-specific PD-1+ T cells.
• Comparison of anti-PD-1 mAbs with and without Fc-binding capability.

Main Results:

• Anti-PD-1 mAb significantly reduced AS plaque size in patients.
• Activated, pro-inflammatory PD-1+ T cells were identified within AS plaques.
• Anti-PD-1 mAb with Fc-binding capability reduced AS plaque size, while that without Fc-binding capability did not.

Conclusions:

• T cell-targeting immunotherapy, specifically anti-PD-1 mAb with Fc-binding capability, can effectively reduce atherosclerosis plaque size.
• The mechanism involves the suppression of pro-inflammatory T cells via interaction with myeloid Fc gamma receptors.
• This study suggests a novel therapeutic strategy for resolving atherosclerosis in humans.