Fig. 5: CEACAM5 levels and intratumoural changes in CD8 + T cells and PDCD1 gene expression. | Nature Communications

Fig. 5: CEACAM5 levels and intratumoural changes in CD8 + T cells and PDCD1 gene expression.

From: CEA-CD3 bispecific antibody cibisatamab with or without atezolizumab in patients with CEA-positive solid tumours: results of two multi-institutional Phase 1 trials

Fig. 5

a CEACAM5 level vs best overall response according to Response Evaluation Criteria in Solid Tumors version 1.1 in the 100–160 mg cibisatamab cohort (MSS-CRC population) including all patients who received at least one dose of any study treatment (medians shown as middle lines, quartiles as boxes, and ranges as bars). b–f Refer to changes between baseline and on-treatment samples from patients with MSS-CRC in S2 who received doses ≥ 100 mg cibisatamab, by best overall response. b Dual chromogenic IHC for CD8 (yellow) and Ki67 (purple nuclear signal, outlining most tumour cells) for a patient with partial response (upper panel) and a patient with stable disease (lower panel). Scale bar represents 88.5 μm (top left), 77.3 μm (top right), 84.4 μm (bottom left) and 73.0 μm (bottom right). c Changes in CD8 + T cells between baseline and on-treatment tissue were quantified with a KI57/CD8 duplex assay. d Single chromogenic IHC for PD-1 at baseline (left) and on-treatment (right). Scale bar represents 76.7 μm (left) and 77.4 μm (right). e Changes in PDCD1 gene expression between baseline and on-treatment tissue were quantified by RNAseq. f Cibisatamab induces tissue pharmacodynamic changes. IHC for CD8 (yellow) and Ki67 (purple, outlining most tumour cells). The immune-excluded immunophenotype is shown on the left (baseline sample) and the immune-inflamed immunophenotype is shown on the right (on-treatment sample). Scale bar represents 65.4 μm (top left), 60.2 μm (top right), 64.4 μm (middle left), 52.8 μm (middle right), 64.5 μm (bottom left), and 61.0 μm (bottom right). In panels a, c, e, blue colour refers to PR, orange to SD, and red to PD. The N or n refers to individual patients. In subplots (c, e) dots for the same patient are connected by a line. The exploratory test in subplot f is two-sided. Atezo Atezolizumab; BL Baseline tissue; BOR Best overall response; CEACAM5 Carcinoembryonic antigen-related cell adhesion molecule 5; cibi Cibisatamab OT On-treatment tissue; PD Progressive disease; PR Partial response; RPKM Reads per kilobase of transcript per million reads mapped; SD Stable disease.

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