The prognostic impact of programmed cell death ligand 1 and human leukocyte antigen class I in pancreatic cancer

Cancer Med. 2017 Jul;6(7):1614-1626. doi: 10.1002/cam4.1087. Epub 2017 Jun 10.

Abstract

Pancreatic ductal adenocarcinoma (PDA) is associated with an immunosuppressive tumor-microenvironment (TME) that supports the growth of tumors and mediates tumors enabling evasion of the immune system. Expression of programmed cell death ligand 1 (PD-L1) and loss of human leukocyte antigen (HLA) class I on tumor cells are methods by which tumors escape immunosurveillance. We examined immune cell infiltration, the expression of PD-L1 and HLA class I by PDA cells, and the correlation between these immunological factors and clinical prognosis. PDA samples from 36 patients were analyzed for HLA class I, HLA-DR, PD-L1, PD-1, CD4, CD8, CD56, CD68, and FoxP3 expression by immunohistochemistry. The correlations between the expression of HLA class I, HLA-DR, PD-L1 or PD-1 and the pattern of tumor infiltrating immune cells or the patients' prognosis were assessed. PD-L1 expression correlated with tumor infiltration by CD68+ and FoxP3+ cells. Low HLA class I expression was an only risk factor for poor survival. PD-L1 negative and HLA class I high-expressing PDA was significantly associated with higher numbers of infiltrating CD8+ T cells in the TME, and a better prognosis. Evaluation of both PD-L1 and HLA class I expression by PDA may be a good predictor of prognosis for patients. HLA class I expression by tumor cells should be evaluated when selecting PDA patients who may be eligible for treatment with PD-1/PD-L1 immune checkpoint blockade therapies.

Keywords: Biomarker; human leukocyte antigens class I; immunotherapy; pancreatic cancer; programmed cell death ligand 1.

MeSH terms

  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / metabolism*
  • Biomarkers
  • Female
  • Gene Expression
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • Immunohistochemistry
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Macrophages / immunology
  • Macrophages / metabolism
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Pancreatic Neoplasms / diagnosis
  • Pancreatic Neoplasms / immunology*
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / mortality
  • Prognosis
  • Recurrence
  • Survival Analysis
  • Tumor Burden
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology

Substances

  • B7-H1 Antigen
  • Biomarkers
  • Histocompatibility Antigens Class I