Project: Elucidating IFN-γ gene signatures as predictive biomarkers for immunotherapy response in melanoma

With the introduction of immunomodulating antibodies, also known as checkpoint inhibitors, melanoma treatment options have improved significantly. However, their efficacy varies considerably among patients, creating a need for predictive biomarkers to select the most appropriate therapy for each case. Using both bulk and single-cell RNA sequencing (RNAseq) data from formalin-fixed paraffin-embedded (FFPE) tissues, patients will be stratified according to their IFN-γ gene expression profile. Two approaches will be used in this study. Firstly, a retrospective evaluation of IFN-γ related genes in melanoma FFPE samples, correlating their expression with treatment outcome: successful (responder) or not (non-responder). Secondly, it is planned to use single-cell RNAseq to understand the significance of specific immune cells with IFN-γ related genes, obtaining additional information on cell dynamics within the tumour microenvironment.

Results

This project will promote a personalised approach to the treatment of melanoma patients in Latvia, and in the future, the diagnostic technology developed as a result could be adapted to tailor therapies for other malignancies as well. Within the framework of international cooperation, this study will not only contribute to the field of tumour immunology but also to the advancement of precision medicine at Rīga Stradiņš University (RSU).

Project achievements

Project updates by 30 June 2026

1. The ethics committee approval has been received within the specified deadline, ensuring the opportunity to begin collecting and analysing patient tissue material in accordance with ethical standards.
2. The establishment of the patient cohort has begun, and the database currently includes more patients than initially planned. A comprehensive data table has been created comprising 262 anonymized melanoma patients who have received immunotherapy in Latvia since 2017.
3. The systematisation of scientific literature has been completed, resulting in a library of approximately 300 references. These cover the role of genes associated with IFN-γ synthesis not only in melanoma but also in tumours of other localisations, particularly in the context of checkpoint inhibitor use. This comprehensive literature summary will serve as the foundation for a review article to be prepared over the next six months, while also providing a theoretical framework for interpreting and contextualising the study results.
4. Preparation for the pilot study has started. FFPE material from a primary tumour, subcutaneous metastasis, and lymph node of a deceased patient has been identified and will be used in a pilot experiment to optimise the mRNA extraction and sequencing protocol.
5. Patient selection for sequencing analysis has already begun. Five anonymised responders and non-responders have been identified, and their excision material will be used for the first bulk sequencing experiment.