Journal article
Characteristics of TCR repertoire associated with successful immune checkpoint therapy responses
Frontiers in Immunology, Vol.11, Art. 587014
2020
Abstract
Immunotherapies have revolutionized cancer treatment. In particular, immune checkpoint therapy (ICT) leads to durable responses in some patients with some cancers. However, the majority of treated patients do not respond. Understanding immune mechanisms that underlie responsiveness to ICT will help identify predictive biomarkers of response and develop treatments to convert non-responding patients to responding ones. ICT primarily acts at the level of adaptive immunity. The specificity of adaptive immune cells, such as T and B cells, is determined by antigen-specific receptors. T cell repertoires can be comprehensively profiled by high-throughput sequencing at the bulk and single-cell level. T cell receptor (TCR) sequencing allows for sensitive tracking of dynamic changes in antigen-specific T cells at the clonal level, giving unprecedented insight into the mechanisms by which ICT alters T cell responses. Here, we review how the repertoire influences response to ICT and conversely how ICT affects repertoire diversity. We will also explore how changes to the repertoire in different anatomical locations can better correlate and perhaps predict treatment outcome. We discuss the advantages and limitations of current metrics used to characterize and represent TCR repertoire diversity. Discovery of predictive biomarkers could lie in novel analysis approaches, such as network analysis of amino acids similarities between TCR sequences. Single-cell sequencing is a breakthrough technology that can link phenotype with specificity, identifying T cell clones that are crucial for successful ICT. The field of immuno-sequencing is rapidly developing and cross-disciplinary efforts are required to maximize the analysis, application, and validation of sequencing data. Unravelling the dynamic behavior of the TCR repertoire during ICT will be highly valuable for tracking and understanding anti-tumor immunity, biomarker discovery, and ultimately for the development of novel strategies to improve patient outcomes.
Details
- Title
- Characteristics of TCR repertoire associated with successful immune checkpoint therapy responses
- Authors/Creators
- J. Kidman (Author/Creator) - The University of Western AustraliaN. Principe (Author/Creator) - The University of Western AustraliaM. Watson (Author/Creator) - Murdoch UniversityT. Lassmann (Author/Creator) - The Kids Research Institute AustraliaR.A. Holt (Author/Creator) - Canada's Michael Smith Genome Sciences CentreA.K. Nowak (Author/Creator) - The University of Western AustraliaW.J. Lesterhuis (Author/Creator) - The University of Western AustraliaR.A. Lake (Author/Creator) - The University of Western AustraliaJ. Chee (Author/Creator) - The University of Western Australia
- Publication Details
- Frontiers in Immunology, Vol.11, Art. 587014
- Publisher
- Frontiers Media
- Identifiers
- 991005544143507891
- Copyright
- © 2020 The Authors.
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.6 Immunology
- 1.6.214 Checkpoint Inhibition
- Web Of Science research areas
- Immunology
- ESI research areas
- Immunology