Terminal Exhaustion
Gene co-expression module in CD8⁺ T cells
| Category | Exhaustion |
|---|---|
| Genes | 15 |
| Annotation certainty | 5 of 5 |
| Annotation consistency | 10 of 15 genes have a known function matching the annotation |
Why this annotation
Top hub genes are LAG3 and HAVCR2 (TIM-3), two canonical exhaustion checkpoint receptors co-expressed on exhausted CD8 T cells in tumors. CXCR6 marks tissue-resident and exhausted T cells in CRC. CARD16 and CASP1 reflect inflammasome/caspase activity in exhausted cells. CD247 (CD3ζ), CD8A, CD8B, CD2 confirm CD8 T cell identity. CHST12 (sulfotransferase) and GBP2 (IFN-stimulated) are consistent with chronic activation. RBCK1 (ubiquitin E3 ligase) and SNAP47 (vesicle fusion) support chronic inflammatory signaling. The co-expression of LAG3+TIM-3+CXCR6 is a well-established exhaustion signature in CRC tumors.
Genes
ACP5, CARD16, CASP1, CD2, CD247, CD8A, CD8B, CHST12, CXCR6, GBP2, HAVCR2, LAG3, RBCK1, SNAP47, TYMP
Most correlated modules
- Cytotoxic Exhausted CD8 · correlation 0.86
- BATF-driven Activation · correlation 0.83
- Tumor mediated exhaustion · correlation 0.83
- Stress-ISG Response · correlation 0.82
- Gut Tissue Residency · correlation 0.81
- Cytotoxic Effector · correlation 0.73
- Cytotoxic Gut Effector · correlation 0.71
Module annotations were drafted by a large language model from the module's genes, then reviewed and approved by a domain expert. See sources & licences.