Understanding Immune Tolerance and Escape in Gestational Choriocarcinoma Using Single-Cell Transcriptomics and Organoid Co-Cultures

Zoha Fatima; Ishaan Goswami

doi:10.18192/osurj.v5i2.7931

Comprendre la tolérance immunitaire et l’évasion dans le choriocarcinome gestationnel à l’aide de transcriptomique unicellulaire et de co-cultures organoïdes

Auteurs-es

Zoha Fatima University of Ottawa, Ottawa, ON, Canada
Ishaan Goswami University of Ottawa, Ottawa, ON, Canada

DOI :

https://doi.org/10.18192/osurj.v5i2.7931

Résumé

Le choriocarcinome gestationnel (GChC) est une malignité trophoblastique agressive qui présente un degré inhabituel d’évasion immunitaire. Les données émergentes suggèrent que le GChC détourne ces mêmes voies de tolérance pour supprimer les réponses immunitaires cytotoxiques. Ces mécanismes incluent le récepteur de mort programmé 1 (-1) et son ligand, la voie de signalisation du ligand de mort programmé 1 (-L1) ainsi que l’inhibition des cellules tueuses naturelles (NK) médiée par l’antigène leucocytaire humain G (HLA-G). Cependant, les interactions cellulaires précises et les circuits de points de contrôle responsables de la persistance des tumeurs restent mal définis.

Cette proposition de recherche vise à intégrer une stratégie basée sur une seule cellule et un organoïde afin d’identifier et de valider fonctionnellement les mécanismes de tolérance immunitaire que le GChC s’approprie du placenta sain. Le séquençage à ARN unicellulaire des tumeurs GChC archivées et des tissus placentaires à terme résoudra les sous-populations tissulaires et quantifiera l’expression des gènes immunoévasifs. Les modèles d’inférence ligand-récepteur cartographient les réseaux de communication suppressifs entre les trophoblastes tumoraux et les cellules immunitaires maternelles. L’immunofluorescence multiplex spatiale confirmera la localisation anatomique des marqueurs de tolérance et identifiera les zones d’exclusion immunitaire dans le microenvironnement tumoral.

Enfin, les tests de co-culture organoïde–immunité du trophoblaste testeront directement si le blocage de-L1, HLA-G ou d’autres voies identifiées restaure l’activation des lymphocytes T et des cellules NK.En combinant le profilage unicellulaire avec la perturbation fonctionnelle, ce cadre vise à définir les circuits de tolérance immunitaire associés qui permettent l’évasion immunitaire du GChC.

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Publié-e

2026-06-17

Numéro

Vol. 5 No. 2 (2026)

Rubrique

Research Proposals

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