Thanks to funding bodies: National Breast Cancer Foundation, Australia (NBCF)

13/n This was a dream postdoc project — the kind that kept me up late, but lit me up inside.
I grew immensely as a scientist, piecing together fragments of cancer evolution and immune microenvironment. Proud to share what we uncovered
#postdoclife #cancerevolution #GynOncol

12/n The dataset is available through cBioportal. cbioportal.org/study/summar...
Thanks to the cBioportal team!

11/n Incredibly grateful to be co-mentored by the brilliant (& genuinely kind) Sandro Santagata, MDPhD, collaborate with a true legend in the field @rdrapkin8-penn.bsky.social

Huge thanks to all co-authors - science is a team effort!

First for me: learning directly from developer
JiaRenLin

10/n All these coincide with a ⬇️ of total CD8+ T cells, especially in the epithelium. There were⬆️activated & exhausted CD8+ T during the later stages!
One culprit? Chronic IFN (IRDS= Interferon related DNA damage signature) is one of the factors contributing to exhaustion!

9/n
Then a shift towards reduced CD4+/CD8+ T cell-APC interactions!

8/n
👩‍🔬Function fades, but the story unfolds:

TIM3+ Antigen Presenting Cells (APC), reflecting their reduced function at later stages!

3D CyCIF helps us visualize the nearby immune cells!

7/n
As STIC progresses from early to advanced, we see a decline in the NK–cDC1 axis — key players in innate anti-tumor immunity.

Meanwhile, HLA-E expression increases: potential actionable immune evasion mechanism!

Both HLA-A & HLA-E are overexpressed in early STIC epithelium.

6/n
Why don’t most p53 signatures progress to cancer — even though they're common?

💡 Because the immune system is already at work. Innate immune players (NK–cDC1–CTL axis) and tissue-resident memory T cells help keep early lesions in check.

#ImmuneSurveillance matters!

5/n
Cancer doesn’t appear overnight — it builds gradually. Even before tumors form, hallmark pathways are already upregulated in advanced STICs! One standout? IFN signaling — it underpins early HGSOC development. A shift towards chronic IFN, driven by chromosomal instability 🧬

4/n⚡️Precancer evolution! 📷🔦
Incidental STICs might be the "early STICs" — with the potential to evolve into cancer-associated (advanced) STICs as disease progresses.

But what about their immune microenvironment? Almost nothing was known.

Time to map it. 🧬🔬#Pevention

3/n
We have developed a comprehensive resource of multiplexed tissue imaging (CyCIF) and spatial transcriptomic (GeoMx) data to study HGSOC development, from precancer lesions (incidental p53 signatures, incidental STICs and cancer-associated STICs) to invasive cancer.🔬

2/n Nearly 20 years ago, a pivotal discovery reshaped our understanding of HGSOC:

🔍 HGSOC originates in the fallopian tube — not the ovary.

It progresses through p53 signatures and STIC lesions, long before invasive disease appears.

A quiet beginning to a deadly cancer.

11/n Incredibly grateful to be co-mentored by the brilliant (& genuinely kind)
Sandro Santagata MDPhD, collaborate with a true legend in the field @rdrapkin8-penn.bsky.social

Huge thanks to all co-authors - science is a team effort!

First for me: learning directly from developer
JiaRenLin!

10/n All these coincide with a ⬇️ of total CD8+ T cells, especially in the epithelium. There were⬆️activated & exhausted CD8+ T during the later stages!

One culprit? Chronic IFN (IRDS= Interferon related DNA damage signature) is one of the factors contributing to exhaustion!

9/n
Then a shift towards reduced CD4+/CD8+ T cell-APC interactions!