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)1 cells. Defective placentation can lead to recurrent pregnancy loss (RPL)2 or placenta accreta spectrum (PAS)3 disorders. Interaction between Programmed Cell Death Protein 1 (PD-1)4 on NK cells and Programmed Cell Death 1 Ligand (PD-L1)5 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)6 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-1+dNK 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.