NY-ESO-1- and survivin-specific T-cell responses in the peripheral blood from patients with glioma

Cancer Immunol Immunother. 2018 Feb;67(2):237-246. doi: 10.1007/s00262-017-2066-z. Epub 2017 Oct 20.

Abstract

The prognosis for patients with glioblastoma is grim. Ex vivo expanded tumor-associated antigen (TAA)-reactive T-cells from patients with glioma may represent a viable source for anticancer-directed cellular therapies. Immunohistochemistry was used to test the survivin (n = 40 samples) and NY-ESO-1 (n = 38 samples) protein expression in tumor specimens. T-cells from peripheral blood were stimulated with TAAs (synthetic peptides) in IL-2 and IL-7, or using a combination of IL-2, IL-15 and IL-21. CD4+ and CD8+ T-cells were tested for antigen-specific proliferation by flow cytometry, and IFN-γ production was tested by ELISA. Twenty-eight out of 38 cancer specimens exhibited NY-ESO-1 protein expression, 2/38 showed a strong universal (4+) NY-ESO-1 staining, and 9/40 cancer lesions exhibited a strong (4+) staining for survivin. We could detect antigen-specific IFN-γ responses in 25% blood samples for NY-ESO-1 and 30% for survivin. NY-ESO-1-expanded T-cells recognized naturally processed and presented epitopes. NY-ESO-1 or survivin expression in glioma represents viable targets for anticancer-directed T-cells for the biological therapy of patients with glioma.

Keywords: Cellular therapy; Glioma; Immunotherapy; NY-ESO-1; Survivin; T-cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, Neoplasm / biosynthesis
  • Antigens, Neoplasm / blood
  • Antigens, Neoplasm / immunology*
  • Brain Neoplasms / blood
  • Brain Neoplasms / immunology*
  • Cell Line, Tumor
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes, T-Lymphocyte / immunology
  • Glioblastoma / blood
  • Glioblastoma / immunology*
  • Humans
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / blood
  • Interferon-gamma / immunology
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / blood
  • Membrane Proteins / immunology*
  • Middle Aged
  • Peptides / immunology
  • Peptides / pharmacology
  • Prognosis
  • Survivin / biosynthesis
  • Survivin / blood
  • Survivin / immunology*
  • T-Lymphocytes / immunology*

Substances

  • Antigens, Neoplasm
  • BIRC5 protein, human
  • CTAG1B protein, human
  • Epitopes, T-Lymphocyte
  • Membrane Proteins
  • Peptides
  • Survivin
  • Interferon-gamma