Long acting propranolol and HSP-70 rich tumor lysate reduce tumor growth and enhance immune response against fibrosarcoma in Balb/c mice

Iran J Immunol. 2013 Jun;10(2):70-82.

Abstract

Background: Noradrenaline (NA), the principal neurotransmitter released from sympathetic nerve terminals, influences T-cell maturation, not only directly in developing T cells, but also indirectly, by acting on the thymic nonlymphoid cells. In vitro and in vivo studies have demonstrated the anti-proliferative, anti-migratory, anti-angiogenic and cytotoxic properties of propranolol, β-AR blocker, against various cancers.

Objectives: To evaluate the effect of propranolol on efficacy of HSP-70 rich lysate vaccine in immunotherapy of fibrosarcoma.

Methods: Mouse fibrosarcoma WEHI-164 cells were used to immunize tumor-bearing mice with or without propranolol and HSP-70. Splenocytes proliferation, cytotoxicity activity of the splenocytes, naturally occurring CD4+ CD25high T-reg cells and IFN-γ and IL-4 secretion as well as tumor size, were assessed to describe the anti-tumor immune response.

Results: A significant increase in the level of IFN-γ in the mice vaccinated with WEHI-164 cells enriched with HSP-70 and co-treated with propranolol was observed compared to controls. However, HSP enrichment or propranolol treatment alone did not enhance the immune response as measured by the level of IFN-γ. Likewise, a decrease in tumor growth in the test group (p<0.01) and a significant increase in CTL activity (p<0.05) was observed.

Conclusion: HSP enriched vaccine shows anti-tumor activity, probably due to the modulation of immune responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / administration & dosage*
  • Animals
  • Cancer Vaccines / therapeutic use*
  • Cell Extracts / administration & dosage
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cytotoxicity, Immunologic
  • Female
  • Fibrosarcoma / immunology
  • Fibrosarcoma / therapy*
  • HSP70 Heat-Shock Proteins / administration & dosage*
  • HSP70 Heat-Shock Proteins / immunology
  • Humans
  • Immunotherapy / methods
  • Interferon-gamma / metabolism
  • Interleukin-4 / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Transplantation
  • Norepinephrine / antagonists & inhibitors
  • Propranolol / administration & dosage*
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology
  • Tumor Burden / drug effects

Substances

  • Adrenergic beta-Antagonists
  • Cancer Vaccines
  • Cell Extracts
  • HSP70 Heat-Shock Proteins
  • Interleukin-4
  • Interferon-gamma
  • Propranolol
  • Norepinephrine