A single-cell map of dynamic chromatin landscapes of immune cells in renal cell carcinoma.
Nikos KourtisQingqing WangBei WangErin OswaldChristina AdlerSamvitha CherravuruEvangelia MalahiasLance ZhangJacquelynn GolubovQiaozhi WeiSamantha LemusMin NiYueming DingYi WeiGurinder S AtwalGavin ThurstonLynn E MacdonaldAndrew J MurphyAnkur DhanikMatthew A SleemanScott S TykodiDimitris SkokosPublished in: Nature cancer (2022)
A complete chart of the chromatin regulatory elements of immune cells in patients with cancer and their dynamic behavior is necessary to understand the developmental fates and guide therapeutic strategies. Here, we map the single-cell chromatin landscape of immune cells from blood, normal tumor-adjacent kidney tissue and malignant tissue from patients with early-stage clear cell renal cell carcinoma (ccRCC). We catalog the T cell states dictated by tissue-specific and developmental-stage-specific chromatin accessibility patterns, infer key chromatin regulators and observe rewiring of regulatory networks in the progression to dysfunction in CD8 + T cells. Unexpectedly, among the transcription factors orchestrating the path to dysfunction, NF-κB is associated with a pro-apoptotic program in late stages of dysfunction in tumor-infiltrating CD8 + T cells. Importantly, this epigenomic profiling stratified ccRCC patients based on a NF-κB-driven pro-apoptotic signature. This study provides a rich resource for understanding the functional states and regulatory dynamics of immune cells in ccRCC.
Keyphrases
- transcription factor
- single cell
- oxidative stress
- dna damage
- gene expression
- early stage
- dna binding
- rna seq
- anti inflammatory
- cell death
- end stage renal disease
- signaling pathway
- renal cell carcinoma
- genome wide
- genome wide identification
- high throughput
- ejection fraction
- chronic kidney disease
- newly diagnosed
- pi k akt
- peritoneal dialysis
- prognostic factors
- nuclear factor
- quality improvement
- squamous cell carcinoma
- inflammatory response
- high density
- lymph node
- patient reported
- immune response