Distinct patterns of infiltrating CD8+ T cells in HPV+ and CD68 macrophages in HPV- oropharyngeal squamous cell carcinomas are associated with better clinical outcome but PD-L1 expression is not prognostic

Oncotarget. 2017 Feb 28;8(9):14416-14427. doi: 10.18632/oncotarget.14796.

Abstract

Immunotherapies are beginning to revolutionise treatment paradigms in oncology with monoclonal antibodies (mAb) targeting T-cell co-inhibitory (e.g. PD-1/PD-L1) and co-stimulatory pathways (e.g. CTLA-4/CD28) demonstrating clinical utility. Some clinical studies demonstrate that responsiveness to PD-1/PD-L1 mAb therapy is greater in patients with expression of PD-L1 in the tumour microenvironment. However, robust responses have also been observed in patients with low or absent expression of PD-L1. Using multiplex immuno-fluorescent labelling we sought to determine how infiltration of tumours by CD8+ T-cells, their expression of PD-1, and the expression of PD-L1 on both tumours and CD68 cells (macrophages) correlated with HPV status and outcome in a cohort of 124 oropharyngeal squamous cell carcinomas (OPSCC).

Keywords: PD-L1; checkpoint inhibitor; human papillomavirus; oropharyngeal squamous cell carcinomas; tumour infiltrating lymphocytes.

MeSH terms

  • Antigens, CD / metabolism*
  • Antigens, Differentiation, Myelomonocytic / metabolism*
  • B7-H1 Antigen / metabolism*
  • Biomarkers, Tumor / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Carcinoma, Squamous Cell / immunology*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / virology
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Macrophages / virology
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Oropharyngeal Neoplasms / immunology*
  • Oropharyngeal Neoplasms / metabolism
  • Oropharyngeal Neoplasms / virology
  • Papillomaviridae / physiology*
  • Prognosis
  • Programmed Cell Death 1 Receptor / metabolism
  • Retrospective Studies
  • Survival Rate
  • Tumor Microenvironment

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD68 antigen, human
  • Programmed Cell Death 1 Receptor