Anti-PD-1 Immunotherapy and Radiotherapy for Stage IV Intrahepatic Cholangiocarcinoma: A Case Report

Ze-Long Liu, Xin Liu, Hong Peng, Zhen-Wei Peng, Jian-Ting Long, Di Tang, Sui Peng, Yong Bao, Ming Kuang, Ze-Long Liu, Xin Liu, Hong Peng, Zhen-Wei Peng, Jian-Ting Long, Di Tang, Sui Peng, Yong Bao, Ming Kuang

Abstract

Due to the unsatisfactory robustness of current predictive biomarkers in many cases, application of immunotherapy in advanced cancers with limited treatment options, such as stage IV intrahepatic cholangiocarcinoma (ICC), was quite common. Hence, strategies to enhance the therapeutic effect of immunotherapy or to extend the scope of potential beneficial patients were urgently needed. Combination of radiotherapy and anti-programmed death receptor-1 (PD-1) immunotherapy was a promising one, since they were found to have a synergistic anti-tumor effect in animal models and a couple of patients. We here present a 68-years-old male with chemotherapy-intolerable stage IV ICC, whose primary tumor had low PD-L1 expression level, scarce CD8+ cells in tumor microenvironment, high microsatellite instability (MSI), and high tumor mutation burden (TMB). These biomarkers showed a conflicting prediction of the treatment response and clinical benefit of anti-PD-1 immunotherapy. Combination therapy of anti-PD-1 immunotherapy and radiotherapy was adopted as first-line treatment for the patient. After six cycles of immunotherapy, shrinkage of the primary liver tumor and metastatic lymph nodes happened, alongside with new lung metastasis, which indicated a mixed response. Radiotherapy was then administered to both the liver and lung lesions, accompanied with continued immunotherapy. The combined therapy eventually led to a complete response for both the primary tumor and all metastases without treatment-related adverse effects. The patient has survived for 26 months after the combined therapy and remains tumor-free currently. This case demonstrates the high inconsistency between immunotherapy response biomarkers and the synergetic anti-tumor effect of immunotherapy and radiotherapy in ICC.

Keywords: biomarkers; combination therapy; immunotherapy; intrahepatic cholangiocarcinoma; radiotherapy.

Copyright © 2020 Liu, Liu, Peng, Peng, Long, Tang, Peng, Bao and Kuang.

Figures

Figure 1
Figure 1
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.
Figure 2
Figure 2
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-γ 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.
Figure 3
Figure 3
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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