Dr Signoretti on the Development of Novel Biomarkers in RCC Using Tissue-Based Analyses

Sabina Signoretti, MD, associate pathologist, Brigham and Women's Hospital, co-leader, Kidney Cancer Program, member, Prostate Cancer Program, professor of pathology, Dana-Farber Cancer Institute, Harvard Medical School, discusses research into the development of novel spatial biomarkers in renal cell carcinoma (RCC) utilizing tissue-based in situ analyses.

There is currently an unmet need in the treatment of patients with RCC forbiomarkers to guide treatment selection. Accordingly, the identification of novel, predictive biomarkers for immune checkpoint inhibitors is of considerable interest. In the last few years, multiplex immunofluorescence technology has been increasingly utilized in both hypothesis-driven biomarker research and in clinical settings, Signoretti begins.

Multiplex immunofluorescence technology allows for the simultaneous detection of multiple biomarkers in a single tissue section, Signoretti explains. When coupled with spectral imaging, image-analysis algorithms, and validation by a pathologist, this technology can provide comprehensive information regarding marker distribution and tissue composition, she says. Unlike immunohistochemistry (IHC), which is unable to label more than one marker per tissue section, multiplex immunofluorescence can label up to 7 markers of interest, Signoretti adds. Although IHC is a standard, practical and cost-effective tool for tumor sample assessment, multiplex immunofluorescence may better represent the complex immune microenvironment.

Researchers in the Signoretti lab continue to work on developing these spatial biomarkers using multiplex immunofluorescence in archival tissue. This research has identified several promising biomarkers based on the tumor microenvironment, Signoretti states. However, the reproducibility of findings will need to be independently validated among different clinical trial cohorts, she says. This is a major challenge in the field of biomarker research, as markers discovered in a clinical trial cohort are often not reproducible when they are evaluated in a different context, Signoretti concludes.