Expression pattern of immunosurveillance-related antigen in adult T cell leukaemia/lymphoma

Histopathology. 2018 May;72(6):945-954. doi: 10.1111/his.13461. Epub 2018 Feb 21.

Abstract

Aims: Adult T cell leukaemia/lymphoma (ATLL) is an aggressive malignancy with a poor prognosis. Human leucocyte antigen (HLA) and β2 microglobulin (β2M) serve as key molecules in tumour immunity, and their expression is reduced frequently in tumour cells. Programmed cell death (PD)-1/PD-ligand1 (PD-L1) interactions play a role in escape of tumour cells from T cell immunity. Therefore, this study aimed to determine the clinicopathological relevance of HLA and β2M expressions in ATLL cells and PD-L1 expression in lymphoma or stromal cells and predict the overall survival of patients with ATLL.

Methods and results: We analysed a total of 123 biopsy samples from patients newly diagnosed with ATLL by using immunohistochemical analysis. Of the patients enrolled, 91 (74%) were positive for HLA (in cell membrane, 60 patients), 89 (72%) were positive for β2M (in cell membrane, 54 patients) and 48 (39%) were positive for both HLA and β2M in the cell membrane (HLAm+ β2Mm+ ). No significant clinical differences other than prognosis were found between the HLAm+ β2Mm+ group and the other groups. Immunophenotypical evaluation revealed significantly higher rates of CD30-positive lymphoma cells (P = 0.003) and PD-L1-positive stromal cells in microenvironments (miPD-L1high ) (P = 0.011) of the HLAm+ β2Mm+ group than in the other groups. The HLAm+ β2Mm+ group had a significantly better prognosis that the other groups (P = 0.0096), and patients showing HLAm+ β2Mm+ with miPD-L1high had the most favourable prognosis among all groups.

Conclusions: The membranous expression of HLA and β2M is likely to reflect the immune response and would be useful to predict prognosis before starting ATLL therapy.

Keywords: PD-L1; adult T cell leukaemia/lymphoma; immunophenotype; immunosurveillance; survival.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen / analysis
  • B7-H1 Antigen / biosynthesis
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / immunology*
  • Disease-Free Survival
  • Female
  • HLA Antigens / analysis
  • HLA Antigens / biosynthesis
  • Humans
  • Kaplan-Meier Estimate
  • Leukemia-Lymphoma, Adult T-Cell / immunology*
  • Leukemia-Lymphoma, Adult T-Cell / mortality
  • Leukemia-Lymphoma, Adult T-Cell / pathology*
  • Male
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • beta 2-Microglobulin / analysis
  • beta 2-Microglobulin / biosynthesis

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • HLA Antigens
  • beta 2-Microglobulin