Fig. 4

Conceptual and technical advances in the development of immunotherapy-synergized epitherapy. a Single-cell multi-omics could be applied to studying the epigenetic regulation of antitumor immunity for designing epigenetic-immunotherapy. Identification of biomarkers on TSTs independent of T cell exhaustion is crucial for assessing the overall ICB efficacy in eliciting antitumor immunity. Such process could be assisted via CITE-seq integrating scRNA-seq and scTCR-seq. Likewise, discovery of epigenetic regulators for therapeutic targeting could be facilitated by Perturb-seq integrating CRISPR screening and scATAC-seq, while spatial information of epigenetic drivers of cell differentiation and fate decisions could be obtained via Spatial ATAC-seq. b The extensive use of conventional epidrugs are limited by poor bioavailability, systemic toxicity and lack of selectivity, which could be potentially avoided by advanced drug design and testing platforms and nano-delivery methods. c By identifying specific and sensitive biomarkers, individualized epitherapy could be designed with tailored dosing schedules. CAR chimeric antigen receptor, CITE-seq cellular indexing of transcriptomes and epitopes by sequencing, CRISPR clustered regularly interspaced short palindromic repeats, Perturb-seq CRISPR-mediated genetic perturbations with single-cell RNA sequencing, scMulti-omics single-cell multi-omics, scATAC-seq single-cell assay for transposase-accessible chromatin by sequencing, scTCR-seq single-cell T cell receptor sequencing, KO knock out, OE overexpression, ICB immune checkpoint blockade, scRNA-seq single-cell RNA sequencing, CITE-seq cellular indexing of transcriptomes and epitopes by sequencing, scATAC-seq single-cell assay for transposase-accessible chromatin using sequencing, TIME tumor immune microenvironment, ATAC-seq assay for transposase-accessible chromatin using sequencing, CAR chimeric antigen receptor, TSTs tumor-specific T cells