Cytotoxic Exhausted CD8
Gene co-expression module in CD8⁺ T cells
| Category | Exhaustion |
|---|---|
| Genes | 11 |
| Annotation certainty | 4 of 5 |
| Annotation consistency | 9 of 11 genes have a known function matching the annotation |
Why this annotation
Hub genes include SAMSN1 (adaptor in lymphocyte signaling), TIGIT (co-inhibitory receptor, exhaustion marker), CCL3 (chemokine released upon activation/cytotoxicity), PRF1 (perforin) and GZMB (granzyme B) — canonical cytotoxic effector molecules. PHLDA1 is induced in activated/exhausted T cells, CTSD is a lysosomal protease involved in granule-mediated killing, DUSP4 is a phosphatase upregulated in dysfunctional T cells, CLEC2D is an NK/T cell inhibitory receptor ligand. Together this module captures a cytotoxic CD8 T cell state that co-expresses effector molecules (PRF1, GZMB, CCL3) with inhibitory/exhaustion markers (TIGIT, PHLDA1, DUSP4), consistent with a terminally differentiated or exhausted-effector phenotype seen in CRC tumors. Neighbor modules M60 and M67 also carry exhaustion markers (TOX, PDCD1, CTLA4), reinforcing this interpretation.
Genes
CCL3, CD2BP2, CLEC2D, CTSD, DUSP4, GZMB, NDFIP2, PHLDA1, PRF1, SAMSN1, TIGIT
Most correlated modules
- BATF-driven Activation · correlation 0.91
- Tumor mediated exhaustion · correlation 0.90
- Gut Residence Trm · correlation 0.87
- Terminal Exhaustion · correlation 0.86
- TCR Activation & Modulation · correlation 0.85
- Autophagy Metabolic Stress · correlation 0.85
- Proliferating CD8 T cell · correlation 0.83
- MHC Class II Presentation · correlation 0.82
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.