PMC7485089_01
H&E staining (A, B) and IHC result of CD8 (C,D) and PD-L1 (E,F) for the liver lesion. H&E staining, hematoxylin and eosin staining; IHC, immunohistochemistry; PD-L1, programmed cell death ligand 1.
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F1
Histology of the liver lesion biopsy found numerous tubular structures of adenocarcinoma and a fibrous stoma (Figures 1A,B). T cells (Figures 1C-F). The whole-exome sequencing (WES) data showed high levels of both MSI and TMB (16.9 mutations/Mb), which indicated the potential benefit of immunotherapy.
Immune characterization of the primary tumor before treatment. (A) The heatmap of the ICC case and 36 ICC cases in the TCGA dataset, with the measurement of ImmunoScore, interferon-gamma signaling (Reactome.org), CYT score, Cibersort Absolute Score, TIS, IIS, PD-L1, and PD-1. (B) Plot of the mean Z-scores across this ICC case and 36 ICC cases in TCGA dataset. (C) The absolute immune score shows the components of the immune cells in primary tumor of the ICC case. ICC, intrahepatic cholangiocarcinoma; TCGA, the Cancer Genome Atlas; TIS, T cell Infiltration Score; IIS, Immune Infiltration Score; PD-L1, programmed cell death ligand 1; PD-1, programmed death receptor-1.
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F2
This case was found to have a moderate level of immune infiltration under a comprehensive immune signature (Figures 2A,B). Analysis of immune cell components in the tumor microenvironment using the CIBERSORT algorithm revealed scarce CD8+ cells but a large number of M2 macrophages, which is consistent with the IHC result and indicates an immunodeficient state (Figure 2C).
Imaging of the patient during treatment. (A) The timeline of his clinical course. (B) Imaging shows the change of the liver lesion over time. (C) Imaging of the patient at baseline and the latest follow-up.
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F3
After all, anti-PD-1 immunotherapy (pembrolizumab, at a dose of 200 mg every month) combined with radiotherapy was considered as treatment for the patient, which was initiated in February 2018 (Figure 3A). The size of the liver lesion slightly reduced to 38 x 33 mm but CA-199 was still over 12,000 U/mL (Figure 3B; Table 1). CA-199 was decreased to 4620.49 U/mL (Table 1). Contrast-enhanced computed tomography (CT) scans showed that the liver lesion reduced to 32 x 23 mm (Figure 3B). However, the number of lung metastases increased, which indicated a mixed response to immunotherapy (Figure 3C). All visible tumors reduced in size gradually in the follow-up and the PTCD was removed 3 months later (Figure 3C). CR is achieved in this stage IV ICC case (Figure 3C; Table 1).