De novo priming: driver of immunotherapy responses or epiphenomenon?

Young, A. L., Lorimer, T., Al-Khalidi, S. K. and Roberts, E. W. (2023) De novo priming: driver of immunotherapy responses or epiphenomenon? Essays In Biochemistry, 67(6), pp. 929-939. (doi: 10.1042/EBC20220244) (PMID:37139854) (PMCID:PMC10539938)

Abstract

The introduction of immunotherapy, in particular immune checkpoint inhibition, has revolutionised the treatment of a range of tumours; however, only a minority of patients respond to these therapies. Understanding the mechanisms by which different immune checkpoint inhibitors work will be critical for both predicting patients who will respond and to developing rational combination therapies to extend these benefits further. The initiation and maintenance of anti-tumour T cell responses is a complicated process split between both the tumour microenvironment and the tumour draining lymph node. As understanding of this process has increased, it has become apparent that immune checkpoint inhibitors can act both within the tumour and in the draining lymph node and that they can target both already activated T cells as well as stimulating the priming of novel T cell clones. Currently, it seems likely that immune checkpoint inhibition acts both within the tumour and in the tumour draining lymph node both reinvigorating existing clones and driving further de novo priming of novel clones. The relative contributions of these sites and targets may depend on the type of model being used and the timeline of the response. Shorter models emphasise the effect of reinvigoration in the absence of recruitment of new clones but studies spanning longer time periods examining T cell clones in patients demonstrate clonal replacement. Ultimately, further work is needed to determine which of the diverse effects of immune checkpoint inhibitors are the fundamental drivers of anti-tumour responses in patients.

• Item Type: Articles
• Additional Information: This work was supported by Cancer Research UK [grant number A_BICR_1920_Roberts to E.W.R.].
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Roberts, Dr Ed and Young, Alex
• Authors: Young, A. L., Lorimer, T., Al-Khalidi, S. K., and Roberts, E. W.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Essays In Biochemistry
• Publisher: Portland Press
• ISSN: 0071-1365
• ISSN (Online): 1744-1358
• Published Online: 04 May 2023
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in Essays In Biochemistry 67(6):929–939
• Publisher Policy: Reproduced under a Creative Commons License