Administration of DNA Encoding the Interleukin-27 Gene Augments Antitumour Responses through Non-adaptive Immunity

Area of Science:

• Immunology
• Cancer Research
• Molecular Biology

Background:

• DNA-mediated immunization is a promising cancer immunotherapy strategy.
• Interleukin-27 (IL-27) plays a role in adaptive immunity.
• The function of IL-27 in DNA vaccination against tumors requires further investigation.

Purpose of the Study:

• To investigate if IL-27 DNA administration enhances anti-tumor effects in mice vaccinated with DNA encoding a tumor antigen (β-galactosidase, β-gal).
• To explore the mechanisms by which IL-27 influences the immune response in this context.

Main Methods:

• Mice were immunized with DNA encoding β-gal, with or without IL-27 DNA.
• Cardiotoxin was used to facilitate exogenous gene expression via intramuscular injection.
• Tumor growth, survival, T-cell responses, antibody production, and natural killer (NK) cell activity were assessed.

Main Results:

• IL-27 DNA administration retarded tumor growth and prolonged survival in mice with β-gal-positive tumors.
• IL-27 enhanced YAC-1-targeted cytotoxicity of splenic NK cells, involving STAT3 phosphorylation and perforin expression.
• IL-27 did not increase β-gal-specific CD8(+) T cells or anti-β-gal antibody production.

Conclusions:

• IL-27 DNA administration activates NK cells, augmenting the anti-tumor effects of DNA vaccination.
• The anti-tumor benefits of IL-27 in this model are mediated through non-adaptive immune responses, primarily via NK cell activation.
• IL-27 represents a potential adjuvant for DNA-based cancer immunotherapy.