Decreased cytotoxic T cells and TCR clonality in organ transplant recipients with squamous cell carcinoma

• Published in: NPJ precision oncology Vol. 4; no. 1; p. 13
• Main Authors: Frazzette, Nicholas, Khodadadi-Jamayran, Alireza, Doudican, Nicole, Santana, Alexis, Felsen, Diane, Pavlick, Anna C., Tsirigos, Aristotelis, Carucci, John A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.06.2020; Nature Publishing Group
• Subjects: 631/67/1813/1352; 631/67/327; 631/67/580; 692/699/67/1813/1352; Antigens; Cancer Research; Cytotoxicity; Gene expression; Gene Therapy; Human Genetics; Internal Medicine; Lymphocytes; Medicine; Medicine & Public Health; Oncology; Patients; Skin cancer; Squamous cell carcinoma; Transplants & implants; Tumors
• ISSN: 2397-768X; 2397-768X
• DOI: 10.1038/s41698-020-0119-9

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.