Fig. 6. Macrophages enable modulation of CD8+ T cells by Fc-active anti-TIGIT antibodies in vivo and in vitro.
a, Heat map showing the expression of selected genes across treatments in tumour CD8+ T cells (left). Volcano plots showing gene expression of tumour CD8+ T cells for anti-PD-L1 + anti-TIGIT IgG2a versus control IgG (middle) and anti-PD-L1 + anti-TIGIT IgG2a + anti-CSF-1R versus control IgG (right). b, The frequency of terminally differentiated TOXhigh gp70-tetramer-binding tumour CD8+ T cells as measured using flow cytometry (left). Data are mean ± s.e.m. Statistical analysis was performed using one-way ANOVA with Dunnett’s multiple-comparison test, with the anti-PD-L1 + anti-TIGIT IgG2a group designated as the control group. Right, representative FACS plots from day 7 after treatment from two independent experiments (n = 5 mice) per group. c, The expression of selected genes across treatments in tumour CD4+ Treg cells (left). Volcano plots showing gene expression of tumour CD4+ Treg cells for anti-PD-L1 + anti-TIGIT IgG2a versus control IgG (middle) and anti-PD-L1 + anti-TIGIT IgG2a + anti-CSF-1R versus control IgG (right). For a,c, scRNA-seq analysis of intratumoural CD45+ cells at day 3 after treatment was from one independent experiment (n = 5 mice per group). In the volcano plots, the broken y axis was used to make the y-axis range comparable between treatments. P values were calculated using two-tailed Wilcoxon rank-sum tests (a,c). d,e, The effects of atezolizumab and tiragolumab (tira.) on the co-cultures of CMV-responsive PBMC T cells and M2-polarized (d) or M1-polarized (e) monocyte-derived macrophages as measured by TNF and IL-2 in the supernatant. Data are mean ± s.e.m., representative of two independent experiments with three PBMC donors per experiment. P values were calculated using one-way ANOVA with Tukey’s multiple-comparison test.