Single-cell analyses identify circulating anti-tumor CD8 T cells and markers for their enrichment

The ability to monitor anti-tumor CD8(+) T cell responses in the blood has tremendous therapeutic potential. Here, we used paired single-cell RNA and TCR sequencing to detect and characterize tumor-matching (TM) CD8(+) T cells in the blood of mice with MC38 tumors or melanoma patients using the TCR as a molecular barcode. TM cells showed increased activation compared with nonmatching T cells in blood and were less exhausted than matching cells in tumors. Importantly, PD-1, which has been used to identify putative circulating anti-tumor CD8(+) T cells, showed poor sensitivity for identifying TM cells. By leveraging the transcriptome, we identified candidate cell surface markers for TM cells in mice and patients and validated NKG2D, CD39, and CX3CR1 in mice. 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.

Automated summary

Monitoring anti-tumor CD8(+) T cell responses in the blood has great therapeutic potential. By using single-cell RNA and TCR sequencing, researchers detected and characterized tumor-matching CD8(+) T cells in blood samples of mice and melanoma patients. These cells showed increased activation compared to nonmatching T cells and were found to be less exhausted than their counterparts in tumors. The study also revealed that PD-1 had poor sensitivity for identifying tumor-matching cells, and identified candidate cell surface markers for these cells in mice and patients.