Antigen and checkpoint receptor engagement recalibrates T cell receptor signal strength
Thomas A.E. Elliot, Emma Jennings, David A.J. Lecky, Natasha Thawait, Adriana Flores‐Langarica, Alastair Copland, Kendle M. Maslowski, David C. Wraith, David Bending
Abstract
T cells in relation to TCR signaling strength. We captured how dose- and time-dependent programming of distinct co-inhibitory receptors rapidly recalibrates T cell activation thresholds and visualized the immediate effects of ICB on T cell re-activation. Our findings reveal that anti-PD1 immunotherapy leads to an increased TCR signal strength. We defined a strong TCR signal metric of five genes upregulated by anti-PD1 in T cells (TCR.strong), which was superior to a canonical T cell activation gene signature in stratifying melanoma patient outcomes to anti-PD1 therapy. Our study therefore reveals how analysis of TCR signal strength-and its manipulation-can provide powerful metrics for monitoring outcomes to immunotherapy.