JAML immunotherapy targets recently activated tumor CD8<SUP>+</SUP> T cells

Eschweiler, Simon, Wang, Alice, Ramirez-Suastegui, Ciro, von Witzleben, Adrian, Li, Yingcong, Chee, Serena J, Simon, Hayley, Mondal, Monalisa, Ellis, Matthew, Thomas, Gareth J
et al (show 3 more authors) (2023) JAML immunotherapy targets recently activated tumor CD8<SUP>+</SUP> T cells. CELL REPORTS, 42 (2). 112040-.

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Junctional adhesion molecule-like protein (JAML) serves as a co-stimulatory molecule in γδ T cells. While it has recently been described as a cancer immunotherapy target in mice, its potential to cause toxicity, specific mode of action with regard to its cellular targets, and whether it can be targeted in humans remain unknown. Here, we show that JAML is induced by T cell receptor engagement, reveal that this induction is linked to cis-regulatory interactions between the CD3D and JAML gene loci. When compared with other immunotherapy targets plagued by low target specificity and end-organ toxicity, we find JAML to be mostly restricted to and highly expressed by tissue-resident memory CD8<sup>+</sup> T cells in multiple cancer types. By delineating the key cellular targets and functional consequences of agonistic anti-JAML therapy in a murine melanoma model, we show its specific mode of action and the reason for its synergistic effects with anti-PD-1.

Item Type: Article
Uncontrolled Keywords: CD8-Positive T-Lymphocytes, Lymphocytes, Tumor-Infiltrating, Animals, Humans, Mice, Neoplasms, Cell Adhesion Molecules, Immunotherapy, Junctional Adhesion Molecules
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 18 Apr 2023 08:38
Last Modified: 18 Oct 2023 07:02
DOI: 10.1016/j.celrep.2023.112040
Open Access URL: https://doi.org/10.1016/j.celrep.2023.112040
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3169643