Excited to share the bulk of my thesis work available online today @CancerCell. We sought to dive into the tumor microenvironment of sarcomatoid renal cell carcinomas to better understand what makes RCC tumors susceptible to immunotherapy: sciencedirect.com/science/ar…
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Sarcomatoid RCC is a rare kidney cancer that is hyper-aggressive yet preferentially responsive to checkpoint blockade. We performed scRNAseq, spectral flow cytometry, and spatial transcriptomics on human sRCCs and ccRCCs, with validation by RNAseq of >3,000 RCC tumors. 2/n
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Ultimately, we show that there is increased antibody-tumor reactivity in sRCC compared to ccRCC, providing functional evidence for the importance of humoral immunity in anti-tumor immune surveillance in RCC. 4/n
Aug 7, 2025 · 4:01 PM UTC
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(2) sRCCs exhibit dysregulated iron programs, including overexpression of iron transport genes, ferroptosis-associated programs, and the iron transporter CD44. This raises a hypothesis that iron dysregulation contributes to the preferential immune sensitivity of sRCCs. 5/n
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(3) A 10 gene signature derived from sRCC tumor cells, coined the Genomic Dedifferentiation Signature, captures the paradoxical clinical behavior of sRCC irrespective of sarcomatoid feature presence. 6/n
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GDS-high patients have worse survival outcomes compared to GDS-low yet achieve improved responses to immunotherapy. GDS-low patients conversely achieve improved responses to anti-angiogenic therapy. 7/n
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The GDS represents a new potential biomarker that is negatively prognostic, yet positively predictive in metastatic RCC. (Stay tuned for more on the GDS as a novel biomarker in RCC coming soon!) 8/n
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This project was a huge effort spanning across disciplines. Thank you to those at @RoswellPark especially PhD mentor, Jason Muhitch, and clinical mentor, Eric Kauffman. Many thanks to peers, colleagues, and administrators in Buffalo @UBuffaloMDPhD @UBJSMBS. 9/n
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As always, deeply thankful for continued #BestMentorEver @montypal @COH and many other thought leaders who provided support & feedback throughout the evolution of this work @HaydnKissick @BcellBruno @BraunMDPhD @careyjans @DrChoueiri @tompowles1 #TinaCascone @NazliDizman. 10/n
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Thanks to the amazing editorial team @CancerCell and most importantly, thank you to the patients and their families who donated samples and time with the shared intent of improving the lives of those diagnosed with kidney cancer worldwide @kidneycan @KidneyCancer @IKCCorg 11/n
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Ok that’s it. Hope you enjoy the paper and please wish me luck on my OBGYN shelf exam tomorrow (I’m going to need a lot of luck at this point!) 12/12.
@NeerajKA @DrRanaMcKay @PGrivasMDPhD @WesleyYipMD @Uromigos @TresUramigas
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