By measuring the canonical T cell activation protein CD69 and expression of Cd69 RNA, Ray et al. established a reporter system that could differentiate between chronic and current antigen exposure-driven activation and effector states both in vitro and in vivo. Using this system, they identified a group of cells with high CD69 and Cd69 expression that spanned several UMAP clusters, but was dominant amongst Texeff, where they expressed a “star” effector signature that comprised Cd81, Xcl1, Ccr7, Gzmc, and proliferation-associated genes. Sorting for this signature enriched for high-quality effectors that were present in regressing murine tumors and in samples from human HNSCC.
Contributed by Lauren Hitchings
ABSTRACT: Antitumor immunity is driven by CD8 T cells, yet we lack signatures for the exceptional effectors in tumors, amongst the vast majority of CD8 T cells undergoing exhaustion. By leveraging the measurement of a canonical T cell activation protein (CD69) together with its RNA ( Cd69 ), we found a larger classifier for TCR stimulation-driven effector states in vitro and in vivo . This revealed exceptional 'star' effectors-highly functional cells distinguished amidst progenitor and terminally exhausted cells. Although rare in growing mouse and human tumors, they are prominent in mice during T cell-mediated tumor clearance, where they engage with tumor antigen and are superior in tumor cell killing. Employing multimodal CITE-Seq allowed de novo identification of similar rare effectors amidst T cell populations in human cancer. The identification of rare and exceptional immune states provides rational avenues for enhancement of antitumor immunity. ONE SENTENCE SUMMARY: Parsing T cell activation states using a novel reporter mouse reveals the functional identity of potent anti-tumor CD8 T cells.
Author Info: (1) (2) (3) (4) (5) (6) (7) (8) (9) (10) (11)
Author Info: (1) (2) (3) (4) (5) (6) (7) (8) (9) (10) (11)
