Could OX40 agonist antibody promote activation of the anti-tumor immune response in gastric cancer?

J Surg Oncol. 2018 Apr;117(5):840-844. doi: 10.1002/jso.25001. Epub 2018 Mar 12.

Abstract

Background and objectives: OX40, a membrane-bound molecule of the tumor-necrosis-factor-receptor superfamily, is a critical costimulatory receptor during the immune response, especially to T cells, but studies described their presence of OX-40 on neutrophils and monocytes, suggesting a potential role in the activation of immune response. Our aim was to characterize costimulatory receptors OX40 expression on circulating leukocytes in gastric cancer to identify novel targets for immunotherapy.

Methods: Peripheral blood mononuclear cells were isolated from 24 gastric cancer patients and 34 healthy controls and the expression of costimulatory (OX40) receptors were analyzed on T cells, neutrophil and monocyte using monoclonal antibodies by flow cytometry.

Results: We found that the higher levels of OX40 + T cells, monocytes/OX40+ and neutrophils/OX40+ from gastric cancer patients when compared to controls (P < 0.0001), and also higher levels of OX40+ T cells when compared to stages III and IV (P = 0.02). Percentage levels of total T cells were similar between patients and controls.

Conclusions: OX40 as a therapeutic agent has been investigated in many preclinical tumor models. Our findings suggest that of levels of costimulatory in T cells in GC will direct future studies on the role that costimulatory receptors play in the failure of T cell-mediated immunity.

Keywords: immunotherapy; neoplasm; receptor OX40 (CD134); stomach.

MeSH terms

  • Antibodies, Monoclonal / immunology*
  • Case-Control Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Leukocytes, Mononuclear / immunology*
  • Leukocytes, Mononuclear / metabolism
  • Leukocytes, Mononuclear / pathology
  • Male
  • Middle Aged
  • Monocytes / immunology*
  • Monocytes / metabolism
  • Monocytes / pathology
  • Prognosis
  • Receptors, OX40 / agonists
  • Receptors, OX40 / immunology*
  • Receptors, OX40 / metabolism
  • Stomach Neoplasms / immunology*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology

Substances

  • Antibodies, Monoclonal
  • Receptors, OX40
  • TNFRSF4 protein, human