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HistoGeneX Biomarker Analysis of a Neoadjuvant Atezolizumab Study in Urothelial Carcinoma, a Nature Medicine publication.

In early November, HistoGeneX pathologists published a paper in Nature Medicine, in collaboration with researchers from Barts Cancer Institute, Queen Mary University of London.

This recent publication describes a Phase 2 study investigating two cycles of atezolizumab before cystectomy in 95 patients with muscle-invasive urothelial cancer. The primary endpoint was pathological Complete Response (pCR) and the secondary endpoint included a biomarker analysis. HistoGeneX performed the immunohistochemistry (IHC), multiplex IHC, and image analysis at its global laboratories. Our pathologists, bioinformatics, and imaging scientists performed the analyses of the images.

The biomarker analyses of over 60 paired (pre-treatment vs post-treatment) patient samples offers several conclusions:

  • Pre-existing T cell immunity (measured by panCK-CD8 IHC) correlated with response. Specifically, high expression of intraepithelial CD8+ cells was associated with a pCR rate of 40% compared to a rate of 20% for the patients without CD8+ cells.
  • Responding tumors with an inflamed phenotype contained cells with dual expression of CD8 and Granzyme B (GZMB), performed as a duplex IHC assay. In contrast, inflamed tumors that relapsed showed low expression of CD8 and GZMB.
  • An increase in intraepithelial CD8 levels occurred in responding tumors, which was not the case in relapsing tumors.
  • FAP expression in relapsed tumors and often linked to stromal components, remained high.
  • Tumor mutation burden did not correlate with response.

For questions of our assessment of pathological complete response, or the IHC and multiplex IHC biomarkers and image analysis, please This email address is being protected from spambots. You need JavaScript enabled to view it..

The official press release can be found here.