JAML Immunotherapy Targets Recently Activated Tumor-Infiltrating CD8+ T Cells

Authors

Simon Eschweiler
Alice Wang
Ciro Ramírez-Suástegui
Adrian von Witzleben
Yingcong Li
Serena J Chee
Hayley Simon
Monalisa Mondal
Matthew Ellis
Gareth J Thomas
Vivek Chandra
Christian H Ottensmeier
Pandurangan Vijayanand

Publication Date

2-28-2023

Journal

Cell Reports

Abstract

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

Keywords

Humans, Animals, Mice, Junctional Adhesion Molecules, Cell Adhesion Molecules, CD8-Positive T-Lymphocytes, Neoplasms, Immunotherapy, Lymphocytes, Tumor-Infiltrating

Comments

Supplementary Materials

PMID: 36701231