Targeting the orphan nuclear receptor NR2F6 in T cells primes tumors for immune checkpoint therapy.

ABSTRACT:

Background

NR2F6 has been proposed as an alternative cancer immune checkpoint in the effector T cell compartment. However, a realistic assessment of the in vivo therapeutic potential of NR2F6 requires acute depletion.

Methods

Employing primary T cells isolated from Cas9-transgenic mice for electroporation of chemically synthesized sgRNA, we established a CRISPR/Cas9-mediated acute knockout protocol of Nr2f6 in primary mouse T cells.

Results

Analyzing these Nr2f6^{CRISPR/Cas9 knockout} T cells, we reproducibly observed a hyper-reactive effector phenotype upon CD3/CD28 stimulation in vitro, highly reminiscent to Nr2f6^-/- T cells. Importantly, CRISPR/Cas9-mediated Nr2f6 ablation prior to adoptive cell therapy (ACT) of autologous polyclonal T cells into

SUBMITTER: Klepsch V 

PROVIDER: S-EPMC6961368 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature