Ushering in Integrated T Cell Repertoire Profiling in Cancer

Abstract

Advances in immune profiling techniques have dramatically changed the cancer immunotherapy and monitoring landscape. High-throughput protein and gene expression technologies have paved the way for the discovery of therapeutic targets and biomarkers, and have made monitoring therapeutic response possible through the ability to independently assay the phenotype, specificity, exhaustion status, and lineage of single T cells. Although valuable insights into response profiling have been gained with current technologies, it has become evident that single-method profiling is insufficient to accurately capture an antitumor T cell response. We discuss and propose new methods that combine multiple axes of analysis to provide a comprehensive analysis of T cell repertoire in the fight against cancer.

Keywords: T cells; high-throughput integrated single T cell profiling; immune checkpoint blockade; immune repertoire.

Figure 1.. T cell based cancer immunotherapies.

Current cancer immunotherapies include (1) immune checkpoint blockade (ICPB) by blocking suppression effects of T cell inhibitory molecules; (2) Neo-antigen vaccine by stimulating T cells that recognizing neo-antigen expressing tumor cells, and (3) TCR re-directed adoptive cell transfer (TCR-ACT), by engineering autologous T cells to recognize specific cancer antigens and infuse them back to patients to fight cancer cells.

Figure 2.. Benefits of T cell repertoire profiling in cancer immunology and immunotherapy.

Current methods of T cell repertoire profiling from tumor-infiltrating lymphocytes and peripheral blood mononuclear cell (PBMC) include neo-antigen profiling, single cell gene expression profiling, and immune repertoire profiling. An integrated immune profiling that combines above all aspects can help to guide a personalized diagnosis, treatment plans and prognosis.