Fig. 3

Therapeutic strategy for anti-Her2 and Palbociclib resistant tumors informed by scRNA-seq analysis. a Enrichment analysis of cabozantinib target genes across single TILs grouped and plotted by different phenotypes (left) or by different immune cell types (right) as annotated in Fig. 2b. b Expression distribution of Kit and Met on t-SNE plot (left) and quantification of Kit and/or Met expressing cells among different immune cell types (right). c Abundance of Kit and/or Met expressing IMCs among tumors with different phenotypes. d Growth of APR tumors with Ab + Cabo treatment (n = 7 for Ab + Pal, n = 6 for Cabo and n = 7 for Ab + Cabo). e Representative images and quantification of CD3 immunohistochemistry staining for tumors with Ab + Pal or Ab + Cabo treatment. Scale bar, 20 μm. Error bars represent SEM. f T-cell depletion during Ab + Cabo treatment against APR tumors. g Relative volumes of APR tumors after treatment with Cabo and ICB. APR tumors were transplanted to recipient MMTV-neu mice and first treated with Ab + Pal to acquire the resistance phenotype (left), then treated with Ab + Pal (n = 6), Ab + Pal + ICB (n = 6), Ab + ICB (n = 8), Ab + Cabo (n = 5), or Ab + Cabo + ICB (n = 7) for 2 weeks (right). h Growth of APR tumors after sequential treatment with Ab + Pal + ICB and Ab + Cabo + ICB (n = 9). APR tumors were treated with Ab + Pal + ICB for 1 week then switched to Ab + Cabo + ICB treatment for 3 weeks. i Survival time to doubled tumor volume of experiment in g. Cabo, protein kinase inhibitor cabozantinib. ICB, immune checkpoint blockades cocktail with anti-CTLA4 and anti-PD-1 mAb. P-value by Student’s t test in a, e, f, g, by three-sample Chi-square test in b and c, by one-way ANOVA with Tukey’s test in d, by log-rank (Mantel-Cox) test in i