Immune Microenvironment Dynamics and Therapeutic Targets in GIST Revealed by Multi-Omics and Functional Validation - PubMed
5 hours ago
- #multi-omics
- #immune microenvironment
- #GIST
- The tumour immune microenvironment (TIME) significantly influences GIST progression and treatment response.
- Multi-omics analyses, including Mendelian randomization and scRNA-seq, were used to study GIST.
- 18 immune cell phenotypes were identified with causal relationships to GIST (10 risk factors, 8 protective factors).
- 4 plasma metabolites were found to mediate immune cell effects on GIST.
- scRNA-seq revealed dynamic remodelling of the TIME in GIST.
- Genes progressively changing from peritumoral to metastatic tissues were identified, correlating with PD-1 expression.
- MYBL1 and AIF1L were validated as key genes influencing CD8+ T cell function and PD-1 response.
- Knockdown of MYBL1 or overexpression of AIF1L showed synergistic anti-tumour effects with PD-1 blockade.
- The study provides new strategies for combined immunotherapy in GIST.