Exploring lncRNA-mediated immunotherapy resistance in melanoma through spatial analysis

• Grant number: 25/05877-5
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: November 11, 2025
• End date: November 10, 2026
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Miriam Galvonas Jasiulionis
• Grantee: Beatriz Cristina Biz Tonin
• Supervisor: Frank John Slack
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Institution abroad: Harvard University, Boston, United States
• Associated to the scholarship: 23/17737-8 - Identification of lncRNAs with a role in Melanoma progression and resistance to immunotherapy, BP.DD

Abstract

Spatial transcriptomics has emerged as a powerful tool for understanding gene expression dynamics within tissue architecture. This technology is particularly valuable for mapping immune-tumor interactions and gene expression. However, its application remains limited, particularly in the study of long non-coding RNAs (lncRNAs), which are key regulators of gene expression and play critical roles in melanoma progression. This project proposes to leverage the Visium (10x Genomics) platform to identify differentially expressed mRNAs and lncRNAs in tumor cells, immune cells, and stromal components from melanoma samples of patients that respond (responders) or not (refractories) to immune checkpoint inhibitors (ICIs). Bioinformatics analyses will be conducted to select the most relevant lncRNAs associated with resistance mechanisms. The most relevant candidates will be further investigated through ortholog identification in murine models, enabling in vivo functional validation in an immunocompetent environment. Beyond the scientific contributions, this study will be instrumental in introducing and consolidating spatial transcriptomics methodologies in Brazil (Multiusers equipment, EPM/UNIFESP), fostering technical expertise and facilitating access to advanced technologies for local research groups. By integrating spatial transcriptomics with resistance profiling, this study will provide novel insights into the role of lncRNAs in immunotherapy response. The findings will contribute to consolidating spatial transcriptomic methodologies and identifying potential biomarkers and therapeutic targets for melanoma treatment. (AU)