HLA class II expression on tumor cells and low numbers of tumor-associated macrophages predict clinical outcome in oropharyngeal cancer

Head Neck. 2019 Feb;41(2):463-478. doi: 10.1002/hed.25442. Epub 2018 Dec 14.

Abstract

Background: Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is a highly immunogenic tumor and differences in tumor microenvironment might contribute to the improved survival of HPV-positive OPSCC patient.

Methods: A comprehensive multivariate analysis with clinical and immune variables (human leukocyte antigen [HLA] I/II, programmed death ligand 1 (PD-L1), programmed death receptor 1 (PD1), T cells, and macrophages) was performed in 142 OPSCC patients.

Results: We found an inverse correlation between the expression of HLA class II molecules on tumor cells and CD68+ CD163+ tumor-associated macrophages (TAMs). High HLA-DP/DQ/DR expression and low number of TAMs were associated with longer disease-specific survival and disease-free survival (DFS). Furthermore, a new population of CD8+ FoxP3+ T cells was correlated with shorter DFS in multivariate analysis.

Conclusions: \We identified new prognostic markers for patients with oropharyngeal cancer, which can be used for selecting patients that can benefit from immunotherapy.

Keywords: HLA-II; HPV infection; TAMs; microenvironment; oropharyngeal cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • B7-H1 Antigen / metabolism
  • Cohort Studies
  • Disease-Free Survival
  • Female
  • HLA-D Antigens / metabolism*
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Macrophages
  • Male
  • Middle Aged
  • Oropharyngeal Neoplasms / metabolism*
  • Oropharyngeal Neoplasms / mortality
  • Oropharyngeal Neoplasms / therapy
  • Papillomaviridae
  • Papillomavirus Infections / metabolism
  • Papillomavirus Infections / pathology
  • Programmed Cell Death 1 Receptor / metabolism
  • Retrospective Studies
  • Survival Rate
  • Treatment Outcome
  • Tumor Microenvironment

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • HLA-D Antigens
  • Histocompatibility Antigens Class I
  • Programmed Cell Death 1 Receptor