Simultaneous identification and profiling of tumor-specific T cells by mass cytometry
Year: 2018
Type: article
Abstract: Background: immunoSCAPE leverages the high-dimensional immune profiling capabilities of mass cytometry combined with a unique technology for the identification of antigen-specific T-cells to support the development of immunotherapy strategies in cancer and immune-related diseases. In cancer, there is now strong evidence that immunotherapy-mediated tumor rejection can rely on tumor-specific (neoantigen-specific) CD8+ T-cells. Consequently, the discovery of neoantigens becomes valuable for personalized cancer immunotherapies. Although in silico pipelines exist, that are capable of predicting non-synonymous mutations potentially giving rise to tumor-specific neoantigens, it is not clear how accurate these methods are in identifying immunogenic and therapeutically relevant epitopes, since T-cell epitope usage can be influenced by many factors. Moreover, analysis of T-cells in cancer patients is challenging as it requires detecting rare antigen-specific T-cell populations in samples that are usually limited in volume and availability. Methods: By applying cytometry by time of flight in conjunction with combinatorial peptide-MHC tetramer staining and high-performance dimensional analysis tools, we are able to map broadly MHC-class I epitope with a high sensitivity for rare antigen-specific T-cells and perform concurrently in-depth characterization of these cells. Results: We will show here the application of this technology in the context of immunotherapy, through the example of a murine in vivo tumor model responsive to checkpoint blockade inhibitors, as well as through the analysis of different human cancer samples. Conclusions: Together, by providing insights into the nature of neoantigen-specific T-cells, immunoSCAPE’s unique target discovery and high-dimensional immune profiling platform is a valuable tool for the development of novel diagnostic biomarkers and therapeutic strategies at different stages of drug development. Legal entity responsible for the study: A*STAR / Singapore Immunology Network and immunoSCAPE. Funding: immunoSCAPE. Disclosure: E. Newell: Board director and shareholder: immunoSCAPE Pte. Ltd. All other authors have declared no conflicts of interest.
Source: Annals of Oncology
Authors: M. Fehlings, E. Newell
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,080
OpenAlex ID: W2898458547