10X single-cell RNASeq profiling of human CD8+ T cells from advanced metastatic melanoma tumor samples and paired peripheral blood

The ability to monitor anti-tumor CD8+ T cell responses in the blood has tremendous therapeutic potential. However, tracking tumor antigen-specific CD8+ T cells in the blood is challenging due to their small number and limited reagents to track these cells. We asked whether paired single-cell RNA and T cell receptor (TCR) sequencing could be used to detect and characterize “tumor matching” (TM) CD8+ T cells in the blood of advanced melanoma patients using the TCR as a molecular barcode. By leveraging the transcriptome, we characterized these cells, and identified candidate cell surface markers for to enrich this population. These data show that the TCR can be used to identify tumor-relevant cells for characterization, reveal unique transcriptional properties of TM cells, and develop marker panels for tracking and analysis of these cells. Overall design: 10X 5' single cell RNASeq and paired TCR sequencing was performed on human CD8+ T cells from advanced metastatic melanoma as well as paired peripheral blood. A paired blood and tumor sample was taken from four different patients prior to checkpoint immunotherapy (treatment naive). For two patients, we also obtained a follow up blood sample after initiating checkpoint therapy. Using the TCR sequence as a molecular barcode, we identified matching T cell receptor clones between the peripheral blood and tumor, characterized the matching versus non-matching T cell populations, and compared these populations within a tissue compartment and between tissue compartments. Please note that the processed data file generated from both GEX and VDJ/TCR samples is linked to the corresponding GEX sample records.