Immune checkpoint inhibitors and reproductive failures

Area of Science:

• Reproductive Immunology
• Immunology
• Cellular Biology

Background:

• The conceptus is a semi-allograft, necessitating immune tolerance mechanisms for successful pregnancy.
• Immune checkpoints are inhibitory pathways regulating immune cell responses and maternal-fetal tolerance.

Purpose of the Study:

• To provide a comprehensive review of immune checkpoints in pregnancy.
• To discuss the roles of CTLA-4, PD-1/PD-L1, TIM-3, LAG-3, and TIGIT in normal and pathological pregnancies.

Main Methods:

• Literature review of immune checkpoints and their functions.
• Analysis of immune checkpoint roles in maternal-fetal tolerance.
• Examination of the impact of immune checkpoint dysregulation on reproduction.

Main Results:

• CTLA-4, PD-1/PD-L1, TIM-3, LAG-3, and TIGIT regulate immune responses and promote maternal-fetal tolerance.
• These checkpoints modulate T cell activity, proliferation, and cytokine production.
• Dysregulation or inhibition of these pathways can compromise reproductive outcomes.

Conclusions:

• Immune checkpoints are vital for successful pregnancy by preventing allograft rejection.
• Understanding these pathways is critical for addressing reproductive complications.
• Immune checkpoint inhibitors may pose risks to human reproduction.