Fig. 3: Anti-PD-1 therapy increases monocyte frequencies and ISG expression within 24 hours. | Nature Medicine

Fig. 3: Anti-PD-1 therapy increases monocyte frequencies and ISG expression within 24 hours.

From: Innate antiviral and immune functions associated with the HIV reservoir decay after anti-PD-1 therapy

Fig. 3: Anti-PD-1 therapy increases monocyte frequencies and ISG expression within 24 hours.

a, The subset of cells labeled ‘Monocytes’ was extracted from scRNA-seq data on PBMCs (Fig. 2g; n = 30; number of samples per timepoint listed in Supplementary Data 1, D3) and analyzed with UMAP and unsupervised clustering in Seurat. The 607 genes most highly expressed after anti-PD-1 treatment were used for clustering, revealing three major clusters. Differential gene expression analyses were performed between C01D02 and C01D01 to identify genes induced after therapy. b, Volcano plots show that, unlike clusters 0 and 1, cluster 2 monocytes exhibited a greater number of genes significantly upregulated at C01D02 versus C01D01, including IFN-inducible genes such as B2M, CD86 and CXCL10. Differential expression was calculated using MAST implemented in Seurat. c, TLR, antiviral and ISG module scores for monocytes were mapped onto the UMAP shown in a. Cluster 2 monocytes displayed reduced TLR module expression and increased ISG/antiviral module expression. In these UMAPs, higher module expression is shown in red, whereas blue indicates lower expression. d, Genes differentially expressed in cluster 2 monocytes (versus all other monocytes) were analyzed using the NicheNet package in R to identify upstream regulators. The analysis was restricted to cytokines measured in plasma. Prioritized ligands—those most strongly correlated with the expression of predicted target genes—are listed to the left. The regulatory potential of these ligands, based on NicheNet’s multistudy reference database, is represented in the heatmap on the right, where deeper purple denotes greater regulatory potential. Details of sample numbers for each analysis and timepoint are provided in Supplementary Data 1, D3. In b, Wilcoxon matched-pairs signed-rank tests were used to assess significant differences from C01D01. Unless otherwise indicated, all statistical tests were two-sided, with multiple comparison adjustments applied where specified; otherwise, exact nominal P values are shown in the figures. FC, fold change; P_val_adj, adjusted P value.

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