Decidual NK cells, extravillous trophoblast and their PD-1/PD-L1 interaction: New insights into recurrent pregnancy loss and placenta accreta spectrum disorders.

[OBJECTIVES] Placentation is influenced by decidual Natural Killer (dNK) cells. Defective placentation can lead to recurrent pregnancy loss (RPL) or placenta accreta spectrum (PAS) disorders. Interaction between Programmed Cell Death Protein 1 (PD-1) on NK cells and Programmed Cell Death 1 Ligand (PD-L1) can alter the cytokine expression and cytotoxic potential of NK cells. This study compares dNK and PD-1 dNK cell number, number of extravillous trophoblast (EVT) and PD-L1 EVTs in two patient groups that experienced either RPL or PAS disorder to a control group.

[METHODS] For this retrospective case-control study tissue from in total 77 abortion samples (healthy women, women with RPL and PAS disorder) were immunohistochemically stained and the above-mentioned cells and receptors were counted and statistically compared between the three groups with either Kruskal Wallis or ANOVA and corresponding posthoc tests.

[RESULTS] The number of EVTs was reduced in the RPL group. There were more dNK and PD-1dNK cells as well as a higher ratio of dNK cells compared to EVTs in the RPL group compared to the control group. Furthermore, the proportion of PD-L1 cells in all EVT cells was higher in the RPL group compared to the control group.

[CONCLUSION] Our findings show that both PD-1 and PD-L1 are differentially expressed on dNK cells and EVTs in the RPL group compared to the control group. Hereby suggesting that PD-1/PD-L1 interaction might influence NK cell function and therefore might be relevant for women experiencing RPL. This may be in terms of cytokine microenvironment or cell-cell-interaction.