Role of NLRP7 in Normal and Malignant Trophoblast Cells

Abstract

Gestational choriocarcinoma (CC) is an aggressive cancer that develops upon the occurrence of abnormal pregnancies such as Hydatidiform moles (HMs) or upon non-molar pregnancies. CC cells often metastasize in multiple organs and can cause maternal death. Recent studies have established an association between recurrent HMs and mutations in the Nlrp7 gene. NLRP7 is a member of a new family of proteins that contributes to innate immune processes. Depending on its level of expression, NLRP7 can function in an inflammasome-dependent or independent pathway. To date, the role of NLRP7 in normal and in malignant human placentation remains to be elucidated. We have recently demonstrated that NLRP7 is overexpressed in CC trophoblast cells and may contribute to their acquisition of immune tolerance via the regulation of key immune tolerance-associated factors, namely HLA family, βCG and PD-L1. We have also demonstrated that NLRP7 increases trophoblast proliferation and decreases their differentiation, both in normal and tumor conditions. Actual findings suggest that NLRP7 expression may ensure a strong tolerance of the trophoblast by the maternal immune system during normal pregnancy and may directly affect the behavior and aggressiveness of malignant trophoblast cells. The proposed review summarizes recent advances in the understanding of the significance of NLRP7 overexpression in CC and discusses its multifaceted roles, including its function in an inflammasome-dependent or independent pathways.

Case Report: First-Line Immune Checkpoint Inhibitor Plus Chemotherapy for Oral Metastasis in a Patient with Ultra High-Risk Gestational Choriocarcinoma

“…Early in the 1970s, Brewer et al 30 proposed that CC was correlated with some immunologic aspects. In recent years, accumulating data 11 , 12 have indicated the ubiquitous overexpression of NLRP7 and PD-L1 in GTN, including CC. NLRP7 contributed to protumoral activities in an inflammasome-independent manner, and its interaction with PD-L1 may play a vital role in immune tolerance and tumor development.…”

“…Currently, the tumor microenvironment has received remarkable attention in cancer research. 10 Increasing literatures 11 , 12 reported NOD-like receptor protein 7 (NLRP7), a member of the NLR, involved in the innate immune response and regulating the expression of programmed cell death-ligand 1 (PD-L1). As the master gene that contributes to trophoblast tumorigenesis, its abnormality facilitates the foundation of immunosuppressive microenvironment.…”

Prognostic prediction of systemic immune-inflammation status for patients with colorectal cancer: a novel pyroptosis-related model

“…However, few studies have investigated the function of NLRP7 in pyroptosis. NLRP7 is overexpressed in gestational choriocarcinoma (CC) trophoblast cells and may function in an inflammasome-dependent or independent pathways [ 19 ]. In our observation, we found that NLRP7 was one of the pyroptosis-associated prognostic biomarkers in CRC.…”

NLRP7 Enhances Choriocarcinoma Cell Survival and Camouflage in an Inflammasome Independent Pathway

“…Even though PHM and CHM are usually benign diseases, patients remain at risk of developing GC. This risk is much higher for patients with CHM (20%) [ 2 ] than for patients with PHM (1.5%) [ 1 , 3 ]. Recent studies have demonstrated that recessive mutations in the inflammatory protein NLRP7 (Nucleotide-binding oligomerization domain, leucine-rich repeat family, Pyrin domain containing 7) are the major cause of recurrent HM [ 2 , 4 , 5 ].…”

“…Depending on the levels of expression of NLRP7, two pathways have been proposed for its function [ 3 ]. While normal levels of NLRP7 have been associated with inflammasome activity, its overexpression has been proposed to function in an inflammasome-independent manner [ 19 ].…”