Document Type : Original Article
Authors
- Ahmad Khalili 1
- Zuhair Muhammad Hassan 1
- Shahram Shahabi 2
- Ali Akbar Pourfathollah 1
- Seyed Nasser Ostad 3
- Shokoofe Noori 4
- Mehdi Mahdavi 5
- Habib Haybar 6
- Ladan Langroudi 1
1 Department of Immunology, School of Medical Sciences, Tarbiat Modares University, Tehran
2 Department of Immunology, Microbiology and Genetics, Faculty of Medicine, Urmia University of Medical Sciences, Urmia
3 Department of Toxicology and Pharmacology Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran
4 Department of Analytical Chemistry, College of Sciences, Shahid Beheshti University
5 Department of Virology, Pasteur Institute of Iran, Tehran
6 Department of Anatomy, Ahwaz University of Medical Science, Ahwaz, Iran
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, antiangiogenic 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, cytotoxic 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.
Keywords