Immunoediting in pregnancy: a new paradigm for understanding fetal tolerance and obstetric disease
Muhammad Adrianes Bachnas, Wiku Andonotopo, Julian Dewantiningrum, Mochammad Besari Adi Pramono, Muhammad Ilham Aldika Akbar, Ernawati Darmawan, Dudy Aldiansyah, I Nyoman Hariyasa Sanjaya, Sri Sulistyowati, Milan Stanojević, Asim Kurjak
Abstract
INTRODUCTION: Pregnancy poses an immunological paradox: the maternal immune system must tolerate a semi-allogeneic fetus while maintaining defense against infections. Rather than being an immunosuppressed state, gestation is now recognized as a dynamic, highly regulated immune condition. CONTENT: This review applies the cancer-derived immunoediting framework - elimination, equilibrium, and escape - to maternal-fetal immune tolerance. We examine how immune checkpoints, regulatory T cells, non-classical MHC molecules, and placental exosomes coordinate to create a localized tolerant environment. Integrating knowledge from oncology and reproductive immunology, this perspective provides a unifying concept for pregnancy immune regulation. SUMMARY: The immunoediting framework reinterprets obstetric disorders such as preeclampsia, recurrent pregnancy loss, and preterm birth as failures of distinct immune phases rather than isolated pathologies. This conceptual shift allows for a broader understanding of how immune balance influences implantation, placental development, and fetal growth. OUTLOOK: Adopting an immunoediting perspective highlights potential clinical advances, including immune checkpoint modulation, regulatory T-cell therapies, and exosome-based biomarkers, paving the way for innovative diagnostic and therapeutic strategies in pregnancy care.