Local Immune Infiltration After Intratumoral Glycopyranosyl Lipid A in Stable-Emulsion Formulation (IT GLA-SE) in Durable Responders
tumor, sarcomas
HEAT, TUMOR, INFILTRATION, SARCOMAS
A, Multiplex immunohistochemical analysis found a detectable increase in CD4 and CD8 T-cell infiltration after treatment with IT GLA-SE. One patient had a detectable increase in CD4 T-cell infiltration from 11% to 34% of all cells counted, in addition to an increase in CD8 infiltration from 0.3% to 3.4%. Another patient had a detectable increase in CD8 T cells (3% to 22% of all cells counted) with a relative decrease in the proportion of T-regulatory cells (scale bars = 100 μm). B, Top clonotypes after IT GLA-SE. Tumor-infiltrating lymphocytes (TILs) were present in 1 patient, with red denoting clonotypes also present in pretreatment TILs. Inset boxes indicate breakdown of specific T-cell receptor (TCR) β DNA sequences coding for same variable amino acid region (red denotes dominant sequence). C, Matched single-cell TCR α and TCR β sequences and their gene expression heat map from posttreatment peripheral blood mononuclear cells. Green and yellow columns on left denote clonotypes expanded in posttreatment TILs. Color bar denotes standardized We investigated whether clinical outcomes were associated with the tumor’s TLR4 expression. We performed TLR4 immunohistochemical analysis across multiple histologic subtypes of banked untreated sarcomas (n = 34); the mean positivity rate was 59% (range, 0%-100%) (eFigure 7A-B in 