Gene expression profile at single cell level of human TILs treated with PD1-TIM3, PD1-LAG3, anti-PD1 or control isotype.. Gene expression profile at single cell level of human TILs treated with PD1-TIM3, PD1-LAG3, anti-PD1 or control isotype.

Several next-generation cancer immunotherapies are designed to target LAG3 and TIM3 checkpoints, though the molecular and cellular mechanisms by which both receptors operate to mediate their anti-tumour effects are still poorly understood. Here, we examined the phenotypical and transcriptional consequences of treatment with bispecific antibodies (bsAbs), currently being tested in clinical trials, which co-target PD1 and either TIM3 or LAG3, respectively, using scRNAseq. Overall design: CD45+ cells were sorted from tumour suspensions from four different patients treated with PD1-TIM3, PD1-LAG3, anti-PD1 or control isotype for 48 and 96 hours. A total of 31 samples was ultimately sequenced from the four different conditions, 2 timepoints and 4 patients (1 sample failed at library preparation).