Abstract
Purpose: Phosphatidylserine (PS) is a phospholipid that is restricted to the cytoplasmic surface of the plasma membrane in most living cells. PS translocates to the cell surface in early apoptosis and inhibits immune responses against self-antigens. PS is also expressed on the surface of living neuroblastoma (NB) cells. The current study examines the effect of blocking NB-associated PS on the T cell responses in vivo and efficacy of a tumor vaccine. Methods: To block PS in vivo NB cells were engineered to secrete Annexin-V (AnV) protein, which specifically binds PS. Western blot was used to determine AnV expression. A/J mice were immunized with 106 γ-irradiated AnV secreting or control NB cells and challenged subcutaneously with WT-NB. ELISPOT was used to determine the frequency of IFNγ producing T cells. Results: Immunization with NB cells secreting AnV led to significantly higher survival than immunization with control cells. To determine the mechanism by which blocking PS improved the efficacy of the vaccine, splenic T cell were isolated and tumor reactivity tested. Mice immunized with AnV secreting cells had significantly higher frequency of T cells producing IFNγ in response to NB than control mice. Conclusions: The study demonstrated that PS inhibited tumor immunity. Blocking NB-associated PS in vivo increased the frequency of tumor reactive T cells and enhanced the efficacy of a tumor vaccine. The findings suggest that anti-PS therapy holds promise for the treatment of NB.
Published Version
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