Immune checkpoint molecules soluble program death ligand 1 and galectin‐9 are increased in pregnancy

Abstract

ProblemPregnancy requires balance between tolerance to the haploidentical fetus and the mother's ability to mount immune responses. There are parallels to this phenomenon that occur in metastatic cancer. We assessed soluble program death ligand‐1 soluble PD‐L1 (sPD‐L1) and galectin‐9 in the blood of pregnant women during gestation as these molecules are highly involved in immune suppression during cancer.Method of studyMaternal blood was collected from 30 primigravida women at monthly intervals during pregnancy, delivery and 6‐week post‐partum. Blood was analyzed for sPD‐L1 and galectin‐9 concentrations by ELISA. Term placentas were collected in formalin and IHC was completed for PD‐L1 and galectin‐9 expression.ResultsMaternal blood levels of sPD‐L1 (0.438 ng/mL) and galectin‐9 (1976 pg/mL) were elevated early in normal pregnancies compared to non‐pregnant controls (0.242 ng/mL and 773 pg/mL, respectively). sPD‐L1 increased throughout gestation, whereas galectin‐9 remained elevated until parturition; both proteins returned to control levels post‐partum. Women carrying male fetuses had significantly higher galectin‐9 levels, but not sPD‐L1, than those carrying females (2263 pg/mL vs 1874 pg/mL; P = .0005). Trophoblast cells of the term placenta coexpress galectin‐9 and PD‐L1.ConclusionImmune‐regulatory molecules galectin‐9 and sPD‐L1 increased during pregnancy and may play a role in immune tolerance that is critical for the fetus.

Liquid biopsy in the era of immuno-oncology: is it ready for prime-time use for cancer patients?

“…Chen et al [126] 30 healthy pregnant patients sPD-L1 increase during normal gestation. Enninga et al [127] neoantigen burden in melanoma patients and is described as a potential novel biomarker for treatment response with pembrolizumab therapy [142]. In a study conducted by Hogan et al using a PCR-based assay to study the CDR3 region of the TCR, they could show that a more clonal TCR repertoire at baseline before anti-PD-L1 therapy was associated with prolonged PFS in melanoma while the a similar clonal TCR repertoire was conversely associated with shorter PFS in patients receiving anti-CTLA4 therapy [139].…”

“…Inflammatory [125], allergic [120], auto-immune [118,124] and infectious diseases [119,121,123], as well as a diabetes [122] can increase PD-L1 levels in the plasma, consequently interfering with its use as a predictive biomarker for ICI therapy (Table 3). Additionally, certain physiological conditions (aging and pregnancy) are also associated with an increase in the plasmatic PD-L1 level [126,127].…”

The Role of B7 Family Molecules in Maternal–Fetal Immunity

“…The epidermal growth factor receptor (EGFR) and JAK2/STAT1 pathways might account for the upregulation of B7-H1 in cytotrophoblasts (51). The maternal blood level of soluble PD-L1 (sPD-L1) is elevated in normal pregnant women at the early stage compared with non-pregnant controls (52). Compared with the findings in peripheral blood, the increased expression of B7-H1 in healthy human decidual CD4 + T cell, Treg, NKT-like, and CD56 + NK cell subsets is accompanied by elevated PD-1 expression in decidual CD4 + T cells, CD8 + T cells, and NKT-like cells.…”

Extracellular vesicles generated by placental tissues ex vivo: A transport system for immune mediators and growth factors

“…CD200, also named OX‐2 membrane glycoprotein, may have a role in macrophage differentiation . CD274 or programmed death‐ligand 1 (PD‐L1) is an immune checkpoint molecule that may have a role in immune suppression during pregnancy . Syncytin‐1 mediates trophoblast fusion and may have a role in tolerance to fetal antigens .…”