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Recombinant Virus-Like Particles Presenting IL-33 Successfully Modify the Tumor Microenvironment and Facilitate Antitumor Immunity in a Model of Breast Cancer

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Document pages: 23 pages

Abstract: Recently, interleukin (IL)-33 has been closely associated witha variety of clinical cancers. IL-33 presents both protumorigenic, and less frequently, antitumorigenic functions depending on disease conditions. IL-33 signaling appears to be a possible target for the treatment of applicable tumor diseases. This study aimed to develop an effective approach to intervene in IL-33 functioning in tumors and reveal the immunotherapeutic potential of anti-IL-33 active immunization. Recombinant truncated hepatitis B virus core antigen (HBcAg), presenting mature IL-33 molecules on the surface of virus-like particles (VLPs), was prepared and used to immunize BALB c mice in a model of murine 4T1 breast cancer. The immunization was performed through either a preventive or therapeutic strategy in two separate studies. Anti-IL-33 immunization with VLPs elicited a persistent and highly titrated specific antibody response and significantly suppressed orthotopic tumor growth and lung metastasis in both studies. The underlying mechanisms might include promoting tumor-specific Th1 CTL cellular responses and the expression of the effector molecule IFN-γ, suppressing Th2 responses, and significantly reducing the infiltration of immunosuppressive Treg cells and MDSCs into tumor tissues in the immunized mice. In conclusion, anti-IL-33 active immunization employing recombinant VLPs as an antigen delivery platform effectively modified the tumor microenvironment and promoted antitumor immunity, indicating the potential of this approach as a new and promising immunotherapeutic strategy for the treatment of cancers where IL-33 plays a definite protumorigenic role.

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