Fig. 2: Dynamic changes of tumour intrinsic and tumour immune microenvironment molecular features in longitudinal biopsies.

RNA sequencing transcriptome profiling was done in mandatory tumour biopsy samples collected before treatment, during rucaparib run-in (run-in), and at C2D1 of rucaparib plus atezolizumab (post-combination). a Schematic of biopsy collection timepoints in relation to treatment schedule. b Summary of enriched pathways (Ingenuity pathway analysis) from significantly differentially expressed genes (≥twofold change, P < 0.05) in paired post-combination vs. pre-treatment biopsies. Orange symbols: upregulated gene pathways; blue symbols: downregulated gene pathways. c Dynamic gene expression levels in the PARPi-regulated pathways for DDR, cell cycle, and apoptosis pathways. d Dynamic expression changes in immune signatures for CD274 (PD-L1 gene) and signatures representing CD8 T-cell activity and cGAS-STING. Each line plot in (c, d) represents a patient with confirmed CR or PR (left-hand panels) or SD or PD (right-hand panels). CnDn Cycle n Day n, cGAS cyclic GMP–AMP synthase, CR complete response, DDR DNA damage repair, OC ovarian cancer, PARPi poly(ADP-ribose) polymerase inhibitor, PD progressive disease, PD-L1 programmed cell death-ligand 1, PFS progression-free survival, PR partial response, SD stable disease, STING stimulator of interferon genes, TNBC triple-negative breast cancer.