High ratio of programmed cell death protein 1 (PD-1)+/CD8+ tumor-infiltrating lymphocytes identifies a poor prognostic subset of extrahepatic bile duct cancer undergoing surgery plus adjuvant chemoradiotherapy

Yu Jin Lim, Jaemoon Koh, Kyubo Kim, Eui Kyu Chie, Bokyong Kim, Kyoung Bun Lee, Jin Young Jang, Sun Whe Kim, Do Youn Oh, Yung Jue Bang, Sung W. Ha

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Background and purpose This study investigated the prognostic role of PD-L1 expression, PD-1+ tumor-infiltrating lymphocytes (TILs), and the ratio of PD-1+/CD8+ TILs in extrahepatic bile duct (EHBD) cancer. Materials and methods We analyzed 83 patients with EHBD cancer who underwent curative surgery plus fluoropyrimidine-based chemoradiotherapy (CRT). Expressions of PD-L1, PD-1, and CD8 were assessed by immunohistochemistry. Results Fifty-six (68%) patients were PD-L1-positive, and its lower expression level was associated with hilar tumor location (P = 0.044). A higher ratio of PD-1+/CD8+ TILs was associated with poorer overall survival (OS) (P = 0.032), relapse-free survival (RFS) (P = 0.024), and distant metastasis-free survival (DMFS) (P = 0.039) in Kaplan-Meier analyses, but survival differences were not observed according to the PD-L1 expression level. With Cox proportional hazards models, the ratio of PD-1+/CD8+ TILs was the independent prognostic factor in OS (HR 2.47, 95% CI 1.04-5.86), RFS (HR 2.41, 95% CI 1.08-5.41), and DMFS (HR 2.67, 95% CI 1.00-7.11) after adjusting for other significant clinicopathologic variables. Conclusion A strong survival impact of the ratio of PD-1+/CD8+ TILs was observed in EHBD cancer. In the poor prognostic subgroup, the blockade of the immune checkpoint in combination with conventional multimodality treatment needs to be considered.

Original languageEnglish
Pages (from-to)165-170
Number of pages6
JournalRadiotherapy and Oncology
Volume117
Issue number1
DOIs
StatePublished - Oct 2015

Keywords

  • Adjuvant chemoradiotherapy
  • Bile duct neoplasms
  • CD8
  • Programmed cell death 1 ligand 1 protein
  • Programmed cell death 1 protein

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