Immunoediting in pregnancy: a new paradigm for understanding fetal tolerance and obstetric disease

J Perinat Med. 2025 Oct 3;54(3):437-454. doi: 10.1515/jpm-2025-0246. Print 2026 Mar 26.

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.

Keywords: exosomes; immunoediting; pregnancy immunology; maternal-fetal interface; pre-eclampsia; regulatory T cells.

Publication types

  • Review

MeSH terms

  • Exosomes / immunology
  • Female
  • Humans
  • Immune Tolerance* / immunology
  • Placenta / immunology
  • Pregnancy
  • Pregnancy Complications* / immunology
  • T-Lymphocytes, Regulatory / immunology