CD45+ cells from human bladder cancer specimens

Background
NK cells are important innate defenders against tumours and have unique abilities to recognize and eliminate cancer cells. Responses to targeted antibody therapeutics are typically limited in bladder tumours, and the functional and immunosuppressive phenotypes of NK cells in this disease are largely unknown.
Methods
Single cell RNA sequencing (scRNAseq) and high-dimensional flow cytometry were used to investigate the phenotype of intratumoural NK cells compared to circulating in patients with bladder cancer.
Findings
NK cells residing within bladder tumours had reduced expression of FcγRIIIa/CD16, the critical receptor for NK-cell-mediated ADCC, on both a transcriptional and protein level. Transcriptional signatures of TGF-β-signalling, a pleiotropic cytokine with known immunosuppressive effects on NK cells, were upregulated in tumour NK cells compared to the blood. In concert, a high TGF-β signature expression also correlated with worse survival and CD16 downregulation. We ...