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

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

Authors

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

Abstract

Gestational choriocarcinoma (GChC) is an aggressive trophoblastic malignancy that displays an unusual degree of immune evasion. Emerging data suggest that GChC hijacks these same tolerance pathways to suppress cytotoxic immune responses. These mechanisms include programmed death receptor 1 (PD-1) and its ligand, programmed death ligand 1 (PD-L1) signaling pathway and human leukocyte antigen G (HLA-G)-mediated Natural killer (NK) cell inhibition. However, the precise cellular interactions and checkpoint circuits responsible for tumour persistence remain poorly defined.

This research proposal aims to integrate a single-cell and organoid-based strategy to identify and functionally validate the immune-tolerance mechanisms that GChC appropriates from the healthy placenta. Single-cell RNA sequencing of archived GChC tumours and term placental tissues will resolve tissue subpopulations and quantify the expression of immune evasive genes. Ligand–receptor inference models will map suppressive communication networks between tumour trophoblasts and maternal immune cells. Spatial multiplex immunofluorescence will confirm the anatomical localization of tolerance markers and identify immune-exclusion zones within the tumour microenvironment. Finally, trophoblast organoid–immune co-culture assays will directly test whether blockade of PD-L1, HLA-G, or other identified pathways restores T-cell and NK-cell activation.

By combining single-cell profiling with functional disruption, this framework aims to define the associated immune-tolerance circuits that enable GChC immune escape. These insights could inform biomarker development and guide selective immunotherapeutic strategies that target tumour- specific tolerance without disrupting normal pregnancy physiology.

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Published

2026-06-17

Issue

Vol. 5 No. 2 (2026)

Section

Research Proposals

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