Expansion of anti-mesothelin specific CD4+ and CD8+ T cell responses in patients with pancreatic carcinoma

PLoS One. 2014 Feb 10;9(2):e88133. doi: 10.1371/journal.pone.0088133. eCollection 2014.

Abstract

We aimed to assess the status of naturally occurring CD4(+) and CD8(+) T cell responses to a tumour associated antigen, Mesothelin, in patients with pancreatic carcinoma and study the effects of elevated IL-10 on Mesothelin-specific T cell responses. For that sake, short term T cell lines were generated from PBMCs of 16 healthy controls, 15 patients with benign pancreatic diseases and 25 patients with pancreatic carcinoma and Mesothelin-specific CD4(+) and CD8(+) T cell responses were analysed using intracellular cytokine assays for IFN-γ. Plasma levels of IL-10 and Mesothelin were measured using cytometric bead array and ELISA assay, respectively. The blocking assays were performed to assess the effects of IL-10 on Mesothelin-specific T cell responses. Here, we demonstrate that the plasma levels of Mesothelin and IL-10 are significantly increased in patients with pancreatic carcinoma. Additionally, we found that (a) Mesothelin-specific T cell responses are significantly expanded in cancer patients (p = 0.0053), (b) the multifunctional CD4(+) T cell response is directed toward a broad repertoire of epitopes within the Mesothelin protein. (c) Mesothelin-specific CD4+ T cell response is directly inhibited by elevated IL-10 in cancer patients. These data provides evidence for the use of Mesothelin as an immunogen for tumour-specific T cell response.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amino Acid Sequence
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Demography
  • GPI-Linked Proteins / blood
  • GPI-Linked Proteins / chemistry
  • GPI-Linked Proteins / immunology*
  • Humans
  • Interferon-gamma / biosynthesis
  • Interleukin-10 / blood
  • Mesothelin
  • Middle Aged
  • Molecular Sequence Data
  • Pancreatic Neoplasms / blood
  • Pancreatic Neoplasms / immunology*
  • Peptides / chemistry
  • Peptides / immunology

Substances

  • GPI-Linked Proteins
  • Peptides
  • Interleukin-10
  • Interferon-gamma
  • Mesothelin

Supplementary concepts

  • Pancreatic Carcinoma