Circulating T-Cell Response
inflammation, tumor, tumor necrosis, death
REGRESSION, INFLAMMATION, TUMOR, TUMOR NECROSIS
We were interested in whether TCR sequences dominant in TILs became more prevalent in the circulation as part of a systemic antitumor response. The PBMCs from all patients underwent TCR sequencing before and after completion of study treatment. Of particular interest was 1 patient who had a complete local response with no radiographically detectable lesion at the end of the trial period (making posttreatment biopsy impossible). After localized injection with IT GLA-SE, the overall circulating PBMC clonality increased 5-fold (0.057 to 0.279). Three clones were present in the pretreatment TILs and PBMCs; these clones underwent clonal expansion in the posttreatment PBMCs and represented 11% of all circulating TCRs (supporting data in eFigure 10 in Because 1 patient had dominant clones with markers for TWe then asked whether the T cells with convergent TCRs constituted a functional effector population. To test this, PBMCs from durable local responders were stimulated with CD3/CD28 beads and then sorted using intracellular staining for tumor necrosis factor α and granzyme B along with CD4 and CD8 labeling (eFigure 11 in We sought to test for a difference in inflammatory proteins and circulating checkpoints in durable responders to evaluate whether this was different compared with minimal responders following IT GLA-SE treatment. Indeed, there were increased markers of both inflammation and checkpoint markers in the responders. For instance, 1 patient with complete regression of treated tumor had a log-fold increase of 0.6 for CD28, 0.6 for lymphocyte activation gene 3 protein, and 0.4 for programmed cell death ligand 1, whereas another patient (with best local response of −17%) had log-fold changes of 0.1, −0.1, and 0, respectively (eFigure 12 in 