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Distinct PD-L1/PD1 Profiles and Clinical Implications in Intrahepatic Cholangiocarcinoma Patients with Different Risk

Jia-Cheng Lu1,2, Hai-Ying Zeng3, Qi-Man Sun1

  • 1Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai 200032, P.R. China.

Theranostics
|August 2, 2019
PubMed

Insights

Immune checkpoint inhibitors targeting PD1/PD-L1 show potential in intrahepatic cholangiocarcinoma (ICC). High PD1/PD-L1 signaling is linked to poorer prognosis in HBV-related ICC, but fewer PD1+ T cells may predict response to anti-PD1 therapy.

Area of Science:

  • Oncology
  • Immunology
  • Hepatology

Background:

  • Immune checkpoint inhibitors targeting PD1/PD-L1 have shown efficacy in various cancers.
  • The role of PD1/PD-L1 signaling in intrahepatic cholangiocarcinoma (ICC), particularly with complex etiologies, is not well understood.

Purpose of the Study:

  • To investigate the expression and clinical significance of CD3, PD1, and PD-L1 in intrahepatic cholangiocarcinoma (ICC).
  • To explore the relationship between PD1/PD-L1 signaling, risk factors (HBV infection, hepatolithiasis), and patient prognosis.
  • To assess the potential of PD1/PD-L1 as a biomarker for predicting response to anti-PD1 therapy in advanced ICC.

Main Methods:

  • Analysis of CD3, PD1, and PD-L1 expression in tumor tissues from 320 ICC patients with diverse risk factors.
  • Retrospective analysis of 7 advanced ICC patients treated with a PD1 inhibitor.
  • Correlation of PD1/PD-L1 expression with clinicopathological features, risk factors, and patient survival.

Main Results:

  • PD-L1 was primarily expressed on tumor cells, while CD3 and PD1 were found on infiltrating lymphocytes.
  • PD1/PD-L1 signaling was activated in ICC tissues, correlating positively with HBV infection and lymph node invasion.
  • Higher PD1+ T cell counts and PD-L1 expression were associated with poorer prognosis in HBV-related ICC but not in hepatolithiasis-related ICC.
  • Multivariate analysis identified PD1/PD-L1 expression as an independent prognostic indicator for ICC.
  • Advanced ICC patients with HBV infection and lower PD1+ T cell counts showed a favorable response to anti-PD1 therapy.

Conclusions:

  • Hyperactivated PD1/PD-L1 signaling serves as a negative prognostic marker in resected ICC.
  • Distinct PD1/PD-L1 expression profiles exist between HBV infection-related and hepatolithiasis-related ICC.
  • PD1+ T cells can potentially serve as a biomarker for prognosis and predicting anti-PD1 immunotherapy efficacy in HBV-infected ICC patients.
Keywords:
hepatitis B virushepatolithiasisimmune checkpoint blockageintrahepatic cholangiocarcinomaprogrammed cell death protein 1programmed cell death protein ligand 1

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