Decidualization & EMT Similarities

During early pregnancy, the maternal endometrium undergoes a profound transformation known as decidualization to accommodate the implanting embryo. Because the embryo contains paternal DNA, it is semi-allogeneic (genetically distinct from the mother). To prevent the maternal immune system from attacking the fetus, the tissue microenvironment adapts to become locally immunosuppressive. However, at the end of the gestational period, these localized tolerogenic mechanisms are altered to facilitate the expulsion of the fetus.

Our proof-of-concept project supervised by Prof. Amir-Hassan Zarnani hypothesized that solid tumors may hijack these exact evolutionary pathways to evade immune surveillance and facilitate growth.

The Cancer Connection: Epithelial-Mesenchymal Transition (EMT)

As tumors grow and metastasize, cancer cells undergo Epithelial-Mesenchymal Transition (EMT), a process allowing them to lose cell polarity and adhesion, gaining migratory properties.

We wanted to explore whether the genetic pathways that prevent the immune system from rejecting a fetus are similar to pathways that cancer uses to hide from the host’s immune system. If tumors mimic pregnancy-induced immune tolerance, identifying these shared pathways could uncover novel therapeutic targets. The ultimate goal would be to reverse this tumor-induced tolerance or induce pathways at the end of the gestational period, triggering the surrounding tissue and immune system to reject the tumor mass naturally.

Specifically, we used public Genome-Wide Association Study (GWAS) datasets. This computational approach allowed us to systematically evaluate whether a specific set of genes, which are primarily related to the decidualization process, also play an active and significant role in the EMT process.