PD-L1 Expression and a High Tumor Infiltrate of CD8+Lymphocytes Predict Outcome in Patients with Oropharyngeal Squamous Cells Carcinoma

Nora Wuerdemann*, Sibel E. Gultekin, Katharina Puetz, Claus Wittekindt, Christian U. Huebbers, Shachi J. Sharma, Hans Eckel, Anna B. Schubotz, Stefan Gattenloehner, Reinhard Buettner, Ernst-Jan Speel, Jens P. Klussmann, Steffen Wagner, Alexander Quaas

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Carcinogenesis of human papillomavirus (HPV)-related (+) oropharyngeal squamous cell carcinoma (OPSCC) differs from HPV-negative (-) OPSCC. HPV-related immune-escape-mechanism could be responsible for the development and progression of HPV+ tumors and an immunophenotype different from HPV- OPSCC is expected. The purpose of this study was to analyze the expression of programmed cell death protein 1 ligand 1 (PD-L1) and its prognostic relevance in relation to CD8+ tumor infiltrating lymphocytes (TILs) and the major histocompatibility complex (MHC) I expression in OPSCC. We quantified PD-L1 expression on tumor cells (TC) and macrophages and MHC I expression in association to CD8(+)TILs by immunohistochemistry on tissue microarray derived from 171 HPV+/-OPSCC. HPV-status was determined by p16(INK4a)immunohistochemistry/HPV-DNA detection. Presence of CD8(+)TILs, PD-L1 expression on TC, and a more frequent loss of MHC I in HPV+ compared to HPV- OPSCC was detected. A high amount of CD8(+)TILs in the whole cohort and in HPV+ OPSCC and PD-L1 expression on TC in HPV- OPSCC was associated with favorable overall survival. There was a trend for an improved outcome according to PD-L1 expression (macrophages) in HPV+ OPSCC without reaching statistical significance. CD8(+)TILs and PD-L1-expression have prognostic impact in OPSCC and might present useful biomarkers for predicting clinical outcome and personalized therapy concepts.

Original languageEnglish
Article number5228
Number of pages16
JournalInternational journal of molecular sciences
Volume21
Issue number15
DOIs
Publication statusPublished - Aug 2020

Keywords

  • oropharyngeal squamous cell carcinoma
  • human papillomavirus
  • programmed cell death 1 ligand 1
  • CD8-positive T-lymphocytes
  • MHC I
  • macrophages
  • tumor micro-environment
  • prognosis
  • HLA CLASS-I
  • HPV-ASSOCIATED HEAD
  • MHC CLASS-I
  • HUMAN-PAPILLOMAVIRUS
  • PROGNOSTIC BIOMARKER
  • T-CELLS
  • DOWN-REGULATION
  • NECK
  • ASSOCIATION
  • PROTEIN

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