Extended Data Fig. 8: Effects of immune checkpoint therapy (ICT) treatment on immune microenvironment.
A. Proportion of T cell subtypes in scRNA-seq analysis of established iKRAS tumors (tumor volume ~250mm3 prior to treatment initiation) treated with control, anti-PD1, anti-CTLA4, anti-41BB or anti-LAG3 antibody for 4 weeks (n = 3 tumors/group). B. Top gene ontologies from GSEA of differential expression in T cells from anti-41BB and control antibody treated mice (n = 3 mice/group). C. Circos plots of T cell receptor clonotype frequencies and expression states of CD8+ T cells in iKRAS tumors after treatment with control (left) and anti-41BB antibody (right) for 4 weeks. Outer histogram is the frequency of each clonotype. Inner bars show the fraction of cells of particular clonotype in each expression state (colors correspond to the clusters in Extended Data Fig. 8a). Inner dendrograms are the hierarchical clustering of gene expression centroids for each clonotype. D. Multiple-testing corrected 95% binomial confidence intervals on the probability of a cell in each treatment group containing a TCR CD3R sequence which overlaps that of another cluster. (*p < 0.05) E. Violin plots showing CCR7 expression in CD4+, CD8+ and CD4-CD8− T cells. (*p < 0.05 two-sided unpaired Wilcox test) F. Proportion of CD4+, CD8+ and CD4−CD8− T cells with expression of CCR7 (left) and IL2Rβ (right). G. Expression of genes and functional markers on CD3+CD4−CD8− T cells. H. Violin plots showing expression of Stat6, Socs3 and Il1β among myeloid cells from control and anti-LAG3 antibody-treated tumors (n = 3 mice/group). (*p < 0.05 two-sided unpaired Wilcox test) I. Violin plots showing expression of Cxcl10, Stat1, Il10, Mrc1 and Socs3 among myeloid cells from control and anti-41BB antibody-treated tumors (n = 3 mice/group). (*p < 0.05 two-sided unpaired Wilcox test).
