Immuno-phenotyping of tumor-specific CD8 T cells using high-dimensional mass cytometry

Abstract

Abstract There is strong evidence that tumor-specific T cells play a central role in tumor rejection. immunoSCAPE leverages the high-dimensional immune profiling capabilities of CyTOF for the identification of antigen-specific T cells to support the development of immunotherapy strategies. By applying CyTOF in conjunction with combinatorial peptide-MHC tetramer staining and high-performance dimensional analysis tools, we broadly and sensitively map T cell reactivity against MHC-class I epitopes while concurrently performing in-depth characterization of these rare antigen-specific T cells. Here, we have applied our unique capabilities to detect and characterize circulating neoantigen-specific T cells in lung carcinoma patient undergoing atezolizumab treatment. Out of 782 neoantigen candidates, T cell reactivity against 13 unique neoantigens was detected within patients who responded to atezolizumab treatment, while T cells within non-responder patients recognized 7 neoantigens. Additionally, neoantigen-specific CD8 T cells from treatment responders exhibit a differentiated effector phenotype similar to CMV or EBV-specific T cells, whereas neoantigen-specific CD8 T cells from non-responders display a memory-like phenotype, suggesting that the properties of tumor-reactive T cells may be associated with clinical response to anti-PD-L1 treatment. By providing insight into the nature and function of tumor-specific T cells, immunoSCAPE’s unique high-dimensional immune profiling platform is a valuable tool to guide the development of novel immunotherapy strategies through assessment of drug biological activity, definition of mechanism of action, and identification of biomarkers of patient response.