Annals of Surgical Oncology

, Volume 23, Issue 8, pp 2610–2617 | Cite as

Program Death 1 Immune Checkpoint and Tumor Microenvironment: Implications for Patients With Intrahepatic Cholangiocarcinoma

  • Faiz Gani
  • Neeraja Nagarajan
  • Yuhree Kim
  • Qingfeng Zhu
  • Lan Luan
  • Feriyl Bhaijjee
  • Robert A. AndersEmail author
  • Timothy M. PawlikEmail author
Hepatobiliary Tumors



Program death 1 (PD-1) and its ligand (PD-L1) have been identified as potential therapeutic targets for solid and hematologic malignancies. The current study aimed to assess PD-L1 expression in intrahepatic cholangiocarcinoma (ICC) and relate clinical outcomes to its expression.


Formalin-fixed, paraffin-embedded tumor specimens were obtained for patients undergoing surgery at Johns Hopkins Hospital between 1991 and 2011. Immunohistochemistry was used to assess PD-L1 expression in tumor-associated macrophages (TAMs) and within the tumor front (TF).


Of 54 tumor samples analyzed, 34 stained positive for PD-L1 expression on TAMs (TAMs+), and 39 stained positive for PD-L1 expression on cells within the tumor front (TF+). The TF+ patients were less likely to present with metastatic lymph nodes (N1 patients: 26.7 vs 7.7 %; p = 0.011), whereas all tumors with intrahepatic metastasis failed to demonstrate staining for PD-L1 around the tumor front (p = 0.020). Patients with tumors shown to be TAMs+ were less likely to present with multiple lesions (35.0 vs 8.8 %; p = 0.017). Patients with tumors exhibiting PD-L1 expression around the tumor front demonstrated a worse overall survival than TF patients (p = 0.008). Multivariable analysis showed that patients with tumors staining for PD-L1 in the tumor front had a 59.5 % reduced survival (TF− vs TF+: time ratio, 0.405; 95 % confidence interval, 0.215–0.761; p = 0.005).


Expression of PD-L1 was noted among a majority of patients, and PD-L1 expression within the tumor front was associated with a 60 % decreased survival. Future clinical trials are necessary to assess the safety and efficacy of anti-PD-L1 therapies among patients with ICC.


Overall Survival Tumor Microenvironment Cholangiocarcinoma Intrahepatic Cholangiocarcinoma Akaike Information Criterion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Conflict of interest

Dr. Robert A. Anders receives research funding from Bristol-Myers Squibb and Five Prime Diagnostics. The remaining authors have no conflicts of interests.

Supplementary material

10434_2016_5101_MOESM1_ESM.docx (15 kb)
Supplementary material 1 (DOCX 14 kb)


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Copyright information

© Society of Surgical Oncology 2016

Authors and Affiliations

  • Faiz Gani
    • 1
  • Neeraja Nagarajan
    • 1
  • Yuhree Kim
    • 1
  • Qingfeng Zhu
    • 2
  • Lan Luan
    • 2
  • Feriyl Bhaijjee
    • 2
    • 3
  • Robert A. Anders
    • 2
    Email author
  • Timothy M. Pawlik
    • 1
    • 4
    Email author
  1. 1.Department of SurgeryJohn Hopkins University School of MedicineBaltimoreUSA
  2. 2.Division of Gastrointestinal and Liver Pathology, Department of PathologyJohns Hopkins University School of MedicineBaltimoreUSA
  3. 3.Department of PathologyAmeriPath IndianaIndianapolisUSA
  4. 4.Division of Surgical Oncology, Department of Surgery, John L. Cameron Professor of Alimentary Tract SurgeryJohns Hopkins HospitalBaltimoreUSA

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