Spatial Transcriptomics in Melanoma – Dr. Krisztian Homicsko (CHUV), Prof. Raphael Gottardo (UNIL) and Dr. Pierre Moulin (CHUV)

Translational research project on the deconstruction of the spatial architecture of early-stage melanoma response to neoadjuvant PD-1 immunotherapy

This “allocated fund”, made possible by a generous contribution of the ORFEO Foundation, was granted to Dr. Krisztian Homicsko (CHUV),
Prof. Raphael Gottardo (UNIL) and Dr. Pierre Moulin (CHUV) in December 2024 for one year.

The landscape of immunotherapies is evolving rapidly, progressing from metastatic to adjuvant and, more recently, to the neoadjuvant setting. In melanoma, neoadjuvant immunotherapies have demonstrated excellent responses and promising long-term outcomes. Both monotherapy and combination immunotherapies have shown efficacy, yet it remains unclear which patients benefit more from one approach over the other. To date, no single biomarker reliably distinguishes patients who will experience clinical benefit, or determines the most appropriate treatment strategy. 

Given the complexity of the tumor microenvironment, we aim to investigate the spatial architecture of melanoma tumors before and after neoadjuvant immunotherapy, leveraging digital pathology and single-cell spatial transcriptomics. Our approach integrates multiple modalities, combining lower-complexity assays such as H&E staining and multiplex immunohistochemistry with high-resolution spatial transcriptomics. This strategy not only enhances our understanding of the tumor microenvironment, but also facilitates the identification of potential biomarkers. 

Moreover, we aim to translate biomarkers discovered through spatial transcriptomics into conventional pathology imaging methods, ultimately validating our findings in a more widely accessible clinical setting.