Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 218, Issue 4, Pages -Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20200920
Keywords
-
Categories
Funding
- National Institutes of Health [P30 DK063720, R01CA229851, U54CA225088, P01 AI56299, P01 AI39671]
- National Institutes of Health S10 Instrumentation Grant [S10 1S10OD021822-01]
- Parker Institute for Cancer Immunotherapy
- Fund for Innovation in Cancer Informatics
- Cook, Amoroso, and Kelly funds
- National Institute of General Medical Sciences (National Institute of General Medical Sciences or the National Institutes of Health) [T32GM007753]
- National Institutes of Health T32 Training Grant in Gastrointestinal Surgery [5T32DK007573]
- National Science Foundation Graduate Research Fellowship
- National Institute of General Medical Sciences Award [T32GM007753, T32 CA009172]
- Abbvie Sponsored Research Award
Ask authors/readers for more resources
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.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available