SONATINA 8 / NSC

Project title: Interrogation of the antigen presentation dynamics via MHCII in tumor immune evasion through multimodal single-cell sequencing.

In this research project we aim to elucidate the mechanisms underlying antigen presentation via Major Histocompatibility Complex class II (MHC-II) in tumor-activated antigen-presenting cells (APCs) and their contribution to immune evasion. Leveraging innovative molecular biology techniques we seek to comprehensively understand the dynamics of immune responses in the tumor microenvironment. We will employ CRISPR-Cas technology known as ‘molecular scissors’ to switch off individual genes involved in the process of MHC-II antigen presentation. By directed shutdown of a gene of interest, we can observe how its absence or modification affects the cell performance and asses its function.

With this approach, we aim to identify genes essential for MHC-II antigen presentation and obtain insights into their role in the induction of anti-tumor response. We will also utilize multiomic single-cell sequencing, to evaluate the consequences of the “gene shutdown” within individual cells at the gene expression and chromatin accessibility levels simultaneously.

This innovative approach offers a comprehensive view of the molecular landscape within individual cells, shedding light on the regulation of MHC-II antigen presentation machinery in the tumor microenvironment. While this project will be predominantly conducted in vitro, leveraging CRISPR-Cas and single-cell sequencing technologies will provide a foundation for potential continuation in more complex systems, including in vivo models and clinical samples. Elucidating the mechanisms underlying MHC-II antigen presentation in tumor-activated APCs might provide valuable insights into cancer immune evasion mechanisms and contribute to the development of more effective immunotherapeutic strategies.

The total funding of the project is 1 299 153 PLN.