Decreased cytotoxic T cells and TCR clonality in organ transplant recipients with squamous cell carcinoma.
Nicholas FrazzetteAlireza Khodadadi-JamayranNicole DoudicanAlexis SantanaDiane FelsenAnna C PavlickAristotelis TsirigosJohn A CarucciPublished in: NPJ precision oncology (2020)
T-cell landscape differences between cutaneous squamous cell carcinoma (cSCC) tumors in immune competent (SCC in IC) and immunocompromised organ transplant recipients (TSCC in OTR) are unclear. We developed an analytical method to define tumor infiltrating lymphocyte (TIL) phenotype in cSCC from immune competent and immune suppressed patients using single-cell TCR sequencing and gene expression data. TSCC exhibits reduced proportions of cytotoxic and naïve TILs and similar numbers of regulatory TILs. Fewer, more heterogeneous TCR clonotypes are observed in TIL from OTR. Most TCR sequences for top ten clonotypes correspond to known antigens, while 24% correspond to putative neoantigens. OTR show increased cSCC events over 12 months possibly due to reduced cytotoxic T-cells. Our novel method of barcoding CD8+ T-cells is the first providing gene expression and TCR sequences in cSCC. Knowledge regarding putative antigens recognized by TCRs with phenotypic function of T-cells bearing those TCRs could facilitate personalized cSCC treatments.
Keyphrases
- regulatory t cells
- gene expression
- squamous cell carcinoma
- single cell
- dendritic cells
- end stage renal disease
- dna methylation
- newly diagnosed
- rna seq
- chronic kidney disease
- ejection fraction
- lymph node metastasis
- locally advanced
- peritoneal dialysis
- radiation therapy
- electronic health record
- peripheral blood
- patient reported outcomes
- intensive care unit
- deep learning
- genetic diversity
- respiratory failure