Immune Phenotypes in Patients With Invasive Mould Infection Support the Use of PD-1 Inhibition as Potential Treatment...

Area of Science:

• Immunology
• Infectious Diseases
• Oncology

Background:

• Invasive mould infections (IMI) lead to significant mortality and morbidity in at-risk populations.
• Current treatments for IMI are limited, necessitating novel therapeutic strategies.
• Targeting immune checkpoints could potentially reverse immune hyporesponsiveness in IMI.

Purpose of the Study:

• To investigate immune checkpoint expression on immune cells in patients with invasive aspergillosis (IA) and mucormycosis (MU).
• To compare immune cell phenotypes and regulatory molecule expression between IMI patients, healthy controls (HC), and control populations (CP).

Main Methods:

• Prospective, observational study design.
• Multicolour flow cytometry analysis of peripheral blood mononuclear cells (PBMCs).
• Comparison of immune cell subsets and immune-regulatory molecule expression in IA, MU, HC, and CP groups.

Main Results:

• Increased regulatory T cells observed in IA and MU patients compared to HCs.
• Elevated expression of immune checkpoint molecules in IA and MU PBMCs versus HC and CP.
• PD-1 expression was highest in mucormycosis (MU) and invasive aspergillosis (IA) patients, suggesting T-cell exhaustion.

Conclusions:

• The study identifies an immune phenotype consistent with T-cell exhaustion in IMI.
• Potential contributing factors include hematological treatment, underlying disease, and the infection itself.
• PD-1 emerges as a potential therapeutic target for IMI treatment.