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Abstract: SA-PO250

Identification of Pathological Micro-Domains in Renal Carcinoma Biopsies Using High-Resolution Spatial Transcriptomics Signatures

Session Information

Category: Onconephrology

  • 1700 Onconephrology


  • Iyer, Lavanya Muthukrishnan, Evotec SE, Hamburg, Hamburg, Germany
  • Wiechers, Carolin, Evotec SE, Hamburg, Hamburg, Germany
  • Zheng, Menglin, Evotec SE, Hamburg, Hamburg, Germany
  • Strassenburg, Silke, Evotec SE, Hamburg, Hamburg, Germany
  • Neumann, Leonie, Evotec SE, Hamburg, Hamburg, Germany
  • Oliveira Vidal, Ramon, Evotec SE, Hamburg, Hamburg, Germany
  • Seip, Britta, Evotec SE, Hamburg, Hamburg, Germany
  • Samatov, Timur, Evotec SE, Hamburg, Hamburg, Germany
  • Fritsch, Rüdiger, Evotec SE, Hamburg, Hamburg, Germany
  • Andag, Uwe, Evotec SE, Hamburg, Hamburg, Germany

Group or Team Name

  • Spatial Team.

Kidney cancer globally ranks 14th in men, 9th in women, with most prevalence in North America and Europe. Clear cell renal cell carcinoma (ccRCC) arises in the proximal tubular epithelial cells (PTECs) and is currently treated with anti-angiogenic molecules and immune checkpoint inhibitors, leading to increased survival rates in responders. However, not all patients respond to these treatments. Here, we applied high-resolution spatial transcriptomics to biopsies of ccRCC patients, identified known markers of progression and gained novel insights into the micro-environments (ME) of affected kidney tissues.


FFPE tumor and healthy adjacent tissue biopsies from 2 ccRCC patients (ICD-10: C64) (51yr male-“A”, 54yr female-“B”) from Indivumed were assayed using 10x Genomics Visium CytAssist (FFPE human panel) and NanoString CosMx (1000-plex universal human panel, IF staining with CD298/B2M, PanCK, CD45, CD3) platforms.


Initial analysis of Visium data revealed distinct differences between the two ccRCC patient tumors- while both patients showed a clear T cell response, we noted an extensive B cell response exclusively in patient A, whereas patient B showed a high number of proliferating tumor cells with angiogenesis. Within tumor A, we observed a striking correlation of the tissue ME to tumor PTECs function. While immune ME preserved normal PTEC metabolism, stromal ME comprised of fully transformed PTECs, highlighting that spatial ME plays a crucial role in tumor progression in ccRCC. Integrated analysis with a scRNAseq reference and CosMx further revealed rare populations of immune cells along the tumor edge within healthy adjacent tissue.


Overall, our high-resolution spatial transcriptomics data revealed patient-specific disease micro-domains and characterized molecular pathways in kidney cancer progression, paving the way for further analysis on distinct disease progression and unraveling potential therapeutic targets at the individual level.