Fig. 4: Tumor profiling.

A Oncoprint of DNA sequencing data for 20 participants. Tumor: whole exome sequencing (“exome”) or customized panel (“panel”; gene list in Supp. Table 2). Plasma: customized panel (gene list in Supp. Table 3). SLD: change in sum of longest diameter of irradiated lesion. Histology: H&N other: other non-squamous head and neck tumors. Ceralasertib dose in mg BD. RT: radiation dose in Gy. BOR: best overall response (by RECIST: CR complete response, PR partial response, SD stable disease, PD progressive disease). G1: genes involved in G1 cell-cycle checkpoint control. DDR: genes involved in DNA damage repair pathways. B Quantification of tumor-infiltrating lymphocytes (TIL) in H&E sections of available tumors. TIL density was quantified in tumor and stromal regions: 3 tumors with CR/PR and 5 with SD or PD were quantified, whole tumor area lymphocyte count. * = P = 0.036 by two-sided Mann–Whitney test. Source data are provided online. C Volcano plot of differentially expressed genes in on-treatment (pre-fraction 2) vs. baseline tumor biopsies for n = 2 paired tumors. Fold-change of treatment versus control: effect size calculated in DESeq2 R package; p-value: Wald test p-value with Benjamini–Hochberg adjustment. Genes of interest indicated. D Gene set enrichment analysis performed for the data shown in (C) using the “hallmarks” gene set. NES normalized enrichment score, FDR Q False discovery rate Q value, EMT epithelial-mesenchymal transition. E Cell-type deconvolution of RNAseq data for the 2 available paired biopsies using CIBERSORTx. Mean fold-change vs. baseline cell-type scores is shown. Source data are provided online. F Cell-type deconvolution of cell type infiltration using mMCPcounter at day 3 and day 10 after irradiation in a mouse model of head and neck cancer. Animals were treated with 4 fractions of 2 Gy and ATRi 25 mg/kg/day for 7 days, starting 2 h before the first fraction of radiation, 3 animals per group. Mean fold-change in cell-type scores vs. vehicle-treated animals for the same time-point is shown. Error bars = SEM. Source data are provided online.