Skip to main content
. 2023 Dec 7;7(12):e0337. doi: 10.1097/HC9.0000000000000337

FIGURE 7.

FIGURE 7

IFN response capacity correlates with IL-2 restoration after PD-1 blockade. (A) UMAP projection of immune cell populations identified in the cytof staining panel. (B) Single-cell heatmap showing the expression pattern of 12 interferon-stimulated proteins across the immune populations defined in (A). The transformed expression of each protein is scaled as a percentage of maximum expression. (C) Fast-Phenograph was used to define distinct modules of interferon-stimulated proteins. The relative abundance of each module within a given cell subset (size of dots) and the enrichment of the cell subset within a module (color of dots) are shown for the 16 modules. (D) Frequency of CD4 Teff cells positive for interferon-stimulated protein module 6 between anti-PD1, IL-2+IFN-γ+ responder (n=6) and nonresponder (n=4) patients. Boxes show the median, upper, and lower quartile and whiskers extend to 1.5X the interquartile range. Patients were stratified to responder/nonresponders to anti-PD-1 based on their (E) IL-2 (yellow) (R n=13; NR n=12 ) or (F) IFN-γ (green) (R n=11 ; NR n=14 ) HBV-specific T cell FluoroSpot results. Fold change in ISG15 expression in CD4 T cells, CD8 T cells, and myeloid cells was calculated by dividing the mean fluorescent intensity of IFN-β-stimulated cells by that of the unstimulated sample. Nonparametric Mann-Whitney t test was used for the statistical analysis. (G) Correlation between the percent increase in IL-2 production after PD-1 blockade and fold change in ISG15 expression. (H) Correlation between the percent increase in IFN-γ production after PD-1 blockade and fold change in ISG15 expression. Abbreviations: BST2, bone marrow stromal cell antigen 2; CD274, cluster of differentiation 274; CXCL-10, C-X-C motif chemokine 10; DC, dendritic cell; DN, double negative; DP, double positive; IDO, Indoleamine 2,3-dioxygenase; IFI16, interferon gamma inducible protein 16; IFIT3, interferon induced protein with tetratricopeptide repeats 3; IFN-γ, interferon; IRF7, interferon regulatory factor 7; ISG15, interferon stimulated gene 15; MX1, Myxovirus resistance protein 1; NK, natural killer cell; NR, nonresponder; PD-1, programmed cell death protein 1; pDC, plasmacytoid dendritic cell; PKR, protein kinase R; R, responder SOCS1, suppressor of cytokine signaling 1; Treg, regulatory CD4 T cell; UMAP, uniform manifold approximation and projection.