Single-Cell Genomic Approaches for Developing the Next Generation of Immunotherapies

In recent times, developments in genomics, proteomics and single-cell technologies, coupled with advances in allied areas like computing and antibody engineering, have enabled significant progress in drug development. Current drug development platforms, however, take only simplified cellular models or molecular readouts into account at the functional level. This makes it difficult to evaluate the effects of a drug at the broader level in tumors, which are heterogeneous and complex collections of cells..

Immunotherapy has revolutionized cancer treatment in recent years by changing the mindset from that of targeting tumor cells to one involving the rejuvenation of the immune system to attack the tumor. Approaches involving the inhibition of checkpoint regulators like PD-1, its ligand PD-L1 and CTLA-4 are now frequently used in the treatment of some cancers. However, there is a wide range in the efficacies and response of both cancers and patients to such treatments, indicating that the detailed, mechanistic understanding of the working of cells is missing. The need, therefore, is to implement pathways that can not only discover new therapeutic targets but can also assess the effects of therapeutic agents on all the cells and molecular pathways in a tumor and its microenvironment. Recent developments in single-cell technologies are making such complex analyses possible, at high resolution.

This perspective by Yofe et al. discusses the role that single-cell analysis can play in driving drug development and the advantages of adopting single-cell technologies in immunotherapy research.

Read the Nature Medicine article on single-cell genomic approaches for the next generation of immunotherapies.