Chromosomally unstable tumors exhibit increased immune cell infiltration compared to chromosomally stable tumors. This enhanced immune surveillance represents a fitness cost of chromosomal instability that limits tumor growth and malignancy in vivo. [@schubert_cancer_2021]
Definitions
- chromosomal instability
- immune cell infiltration
- tumor
- malignancy
- chromosomally unstable tumors
- immune surveillance
- tumors
- fitness
- in vivo
Synthesis
Chromosomal instability is established to promote immune cell infiltration into tumors, creating an immunogenic environment that exposes chromosomally unstable cancer cells to immune surveillance. This infiltration occurs because the genomic chaos generated by ongoing chromosome missegregation produces heterogeneous neoantigens and stress signals that attract immune cells, as demonstrated both in mouse models and human cancers. However, for chromosomally unstable tumors to achieve malignancy, they must actively suppress this immune response through a conserved mechanism involving Stat1 signaling inactivation combined with Myc activation, which specifically alleviates the chromosomal instability-induced immune infiltration and allows aneuploid cells to persist despite their fitness costs. While the initial immunogenic consequences of chromosomal instability and the subsequent requirement for immune evasion are well-established, the precise molecular signals that trigger initial immune cell recruitment and whether all forms of chromosomal instability generate equally immunogenic environments remain areas requiring further investigation.
Related
- Stat1 inactivation mechanism is conserved between mouse and human aneuploid cancers
- Subclonal driver events determine therapy response and tumor evolution
- Hypoxia-related transcriptional programs are variably expressed in glioblastoma cells
- Aneuploid cancers inactivate Stat1 to circumvent immune surveillance
- Aneuploid tumors inactivate Stat1 signaling with increased Myc activity
- Extra centrosomes correlate with chromosomal instability in tumors
- Stat1 loss combined with Myc activation alleviates CIN-induced immune infiltration
- Single-cell sequencing reveals karyotype heterogeneity in lymphomas
- Glioblastoma cells exhibit continuum of stemness-related expression states
- p53 loss is common but not enriched in chromosomally unstable tumors
- CENP-E reduction generates aneuploidy and chromosomal instability
- Tumors contain multiple subclones with spatial and temporal heterogeneity