Spatial immune landscapes of the human placenta: Biomarkers and therapeutic insights in pregnancy disorders.

Pregnancy disorders, including preeclampsia (PE), placenta accreta spectrum (PAS), and chorioamnionitis (CAM), significantly threaten maternal and fetal health, arising from immune and trophoblast dysregulation within the placental microenvironment. Traditional approaches lack the ability to resolve the spatial organization of these interactions. Spatial profiling technologies such as spatial transcriptomics and proteomics enable high-resolution mapping of gene and protein expression within intact tissue architecture, uncovering disease-specific immune checkpoint alterations, trophoblast invasion patterns, and localized inflammatory responses. These spatial signatures not only advance mechanistic understanding but also reveal candidate biomarkers for early diagnosis and risk stratification, such as reduced PD-L1 expression in PE and excessive checkpoint upregulation in PAS and CAM. In addition, these findings highlight therapeutic opportunities, including immune checkpoint modulation tailored to the placental microenvironment. Looking ahead, integrating spatial profiling with multi-omics and longitudinal analyses will be critical for translating spatial discoveries into precision diagnostics and targeted therapies, ultimately improving maternal-fetal outcomes.