NLRP7 Promotes Choriocarcinoma Growth and Progression through the Establishment of an Immunosuppressive Microenvironment

Cancers

Pierre-Adrien Bolze¹  Padma Murthi²  Rima Slim³  Vincent Sapin⁴  Roland Abi Nahed⁵  Nadia Alfaidy⁵  Christophe Battail⁵  Nicolas Lemaitre⁵  Frederic Sergent⁵  Deborah Reynaud⁵  Pascale Hoffmann⁵  Mohamed Benharouga⁵  Odile Filhol⁵  Wael Traboulsi⁶  Houssine Boufettal⁷  Touria Aboussaouira⁷ 

[1] Department of Gynecological Surgery and Oncology, Obstetrics, French Reference Center for Gestational Trophoblastic Diseases, University Hospital Lyon Sud, University of Lyon 1, 69000 Lyon, France;Department of Pharmacology, Monash Biomedicine Discovery Institute, Monash, Clayton, VIC 3168, Australia;Departments of Human Genetics and Obstetrics and Gynecology, McGill University Health Centre Research Institute, Montréal, QC H4A 3J1, Canada;Genetics, Reproduction and Development (GReD) Laboratory, CNRS UMR 6293, Inserm U1103, Translational Approach to Epithelial Injury and Repair Team, Clermont Auvergne University, 63000 Clermont-Ferrand, France;Institut National de la Santé et de la Recherche Médicale, Inserm U1292, Université Grenoble-Alpes, 38000 Grenoble, France;Laboratory for Immuno-Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 2005, USA;Obstetrics and Gynecology Department, Ibn Rochd University Hospital, Hassan 2 University, Faculty of Medicine and Pharmacy, 20360 Casablanca, Morocco;

关键词: choriocarcinoma;    hydatidiform mole;    NLRP7;    tumor microenvironment;    maternal immune tolerance;    orthotopic model of choriocarcinoma;   

DOI  :  10.3390/cancers13122999

来源: DOAJ

【 摘 要 】

The inflammatory gene NLRP7 is the major gene responsible for recurrent complete hydatidiform moles (CHM), an abnormal pregnancy that can develop into gestational choriocarcinoma (CC). However, the role of NLRP7 in the development and immune tolerance of CC has not been investigated. Three approaches were employed to define the role of NLRP7 in CC development: (i) a clinical study that analyzed human placenta and sera collected from women with normal pregnancies, CHM or CC; (ii) an in vitro study that investigated the impact of NLRP7 knockdown on tumor growth and organization; and (iii) an in vivo study that used two CC mouse models, including an orthotopic model. NLRP7 and circulating inflammatory cytokines were upregulated in tumor cells and in CHM and CC. In tumor cells, NLRP7 functions in an inflammasome-independent manner and promoted their proliferation and 3D organization. Gravid mice placentas injected with CC cells invalidated for NLRP7, exhibited higher maternal immune response, developed smaller tumors, and displayed less metastases. Our data characterized the critical role of NLRP7 in CC and provided evidence of its contribution to the development of an immunosuppressive maternal microenvironment that not only downregulates the maternal immune response but also fosters the growth and progression of CC.

【 授权许可】

Unknown