Tumor mediated exhaustion
Gene co-expression module in CD8⁺ T cells
| Category | Exhaustion |
|---|---|
| Genes | 12 |
| Annotation certainty | 5 of 5 |
| Annotation consistency | 9 of 12 genes have a known function matching the annotation |
Why this annotation
This module is anchored by canonical exhaustion markers: PDCD1 (PD-1), TOX (master regulator of T cell exhaustion), CXCL13 (chemokine highly specific to exhausted/follicular CD8 T cells in tumors), TIGIT-neighbor SIRPG (inhibitory receptor), IFNG (effector cytokine co-expressed in exhausted effectors), ITM2A (expressed in exhausted T cells and early memory). HNRNPLL regulates alternative splicing of CD45 in activated T cells. UCP2 reflects metabolic reprogramming. ANXA6 is expressed in terminally differentiated T cells. PTPN7 dampens TCR signaling. GALM and SARDH are metabolic enzymes. The coherent co-expression of TOX, PDCD1, CXCL13, SIRPG, and IFNG makes this a high-confidence exhausted CD8 T cell module, consistent with the tumor-infiltrating exhausted phenotype well-described in CRC. Neighbors M65 and M67 also carry exhaustion markers, reinforcing this neighborhood as an exhaustion cluster.
Genes
ANXA6, CXCL13, GALM, HNRNPLL, IFNG, ITM2A, PDCD1, PTPN7, SARDH, SIRPG, TOX, UCP2
Most correlated modules
- Cytotoxic Exhausted CD8 · correlation 0.90
- BATF-driven Activation · correlation 0.89
- MHC Class II Presentation · correlation 0.89
- ER-Golgi Trafficking · correlation 0.88
- Gut Residence Trm · correlation 0.83
- Autophagy Metabolic Stress · correlation 0.83
- Terminal Exhaustion · correlation 0.83
- Stress-ISG Response · 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.