IL-2Rα-biased, but not βγ-biased, agonist reprograms tumor immune landscape and synergize with αPD-1 therapy

ABSTRACT: We investigated whether exogenous supplies of different IL-2R agonists (IL-2wt, IL-2nα or IL-2α-bias) at the concentration of 3 mg/g body weight could rescue the transcriptional signatures of dysfunctional T cells in large tumors, or allow them to regain sensitivity to αPD-1 antibody. Remarkably, after transient stimulation by IL-2wt, large tumors fully restored the effector/activation signatures observed in small tumors, such as upregulation of effector genes (Gzma, Gzmb, Gzmk and Ifng), T cell activation/exhaustion genes (Ctla4, Pdcd1, Lag3 and Havcr2), inflammatory cytokine/cytokine receptors (Il2ra, Il2rb, Il2rg and Il21r), and chemokines (Cxcl9, Cxcl10 and Ccl19) (Fig.7d). Surprisingly, although IL-2α-bias had >10-fold weaker in vitro activity than IL-2wt, and could only activate the

INSTRUMENT(S): Illumina NovaSeq 6000

ORGANISM(S): Mus musculus

SUBMITTER: Tiongsun Chia 

PROVIDER: E-MTAB-12372 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress