Projects per year
Abstract
Immune checkpoint immunotherapies act to block inhibitory receptors on the surface of T cells and other cells of the immune system. This can increase activation of immune cells and promote tumour clearance. Whilst this is very effective in some types of cancer, significant proportions of patients do not respond to single-agent immunotherapy. To improve patient outcomes, we must first mechanistically understand what drives therapy resistance. Many studies have utilised genetic, transcriptional, and histological signatures to find correlates of effective responses to treatment. It is key that we understand pretreatment predictors of response, but also to understand how the immune system becomes treatment resistant during therapy. Here, we review our understanding of the T-cell signatures that are critical for response, how these immune signatures change during treatment, and how this information can be used to rationally design therapeutic strategies. We highlight how chronic antigen recognition drives heterogeneous T-cell exhaustion and the role of T-cell receptor (TCR) signal strength in exhausted T-cell differentiation and molecular response to therapy. We explore how dynamic changes in negative feedback pathways can promote resistance to single-agent therapy. We speculate that this resistance may be circumvented in the future through identifying the most effective combinations of immunotherapies to promote sustained and durable antitumour responses.
Original language | English |
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Article number | EBC20220247 |
Number of pages | 11 |
Journal | Essays in Biochemistry |
Volume | 2023 |
Early online date | 30 Jun 2023 |
DOIs | |
Publication status | E-pub ahead of print - 30 Jun 2023 |
Bibliographical note
© 2023 The Author(s).Fingerprint
Dive into the research topics of 'T-cell response to checkpoint blockade immunotherapies: from fundamental mechanisms to treatment signatures'. Together they form a unique fingerprint.Projects
- 2 Active
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Regulation of TCR signalling dynamics during T follicular helper cell responses
LISTER INSTITUTE OF PREVENTATIVE MEDICINE
1/10/22 → 30/09/27
Project: Research
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Negative feedback control of T cells in tolerance and cancer - from pathways to biomarkers
1/02/21 → 31/01/26
Project: Research Councils