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

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