Anti-LIF Immunization Inhibits Breast Tumor Growth and Modulates Systemic Cytokines in Mice

Leukemia inhibitory factor (LIF), a member of the IL-6 cytokine family, is a significant tumor-promoting factor in breast cancer, contributing to immune suppression, progression, and therapy resistance. While neutralizing LIF offers a promising therapeutic avenue, the systemic immunological impact of targeting this cytokine remains largely unexplored. This study investigates active immunization against LIF to understand its effects on tumor progression and systemic cytokine responses.

Female BALB/c mice were actively immunized with recombinant LIF protein emulsified in Freund's adjuvant to induce anti-LIF antibodies. After confirming antibody titers, tumors were established via subcutaneous injection of 4T1 breast cancer cells. The study monitored tumor growth as a primary endpoint and measured serum cytokine levels (IFN-γ, TNF-α, IL-6, IL-10, IL-4, and TGF-β) using ELISA. Control mice were not immunized against LIF, allowing for comparison of tumor progression and cytokine profiles.

Active immunization against LIF significantly inhibited tumor growth compared to control groups. Serum analysis revealed a systemic suppression of tumor-induced IL-10 in immunized, tumor-bearing mice. Concurrently, IFN-γ levels were significantly enhanced in these same tumor-bearing mice. > The most important finding was that vaccination against LIF effectively limited tumor progression while selectively modulating systemic cytokine profiles, specifically by suppressing tumor-induced IL-10 and boosting IFN-γ responses. In contrast, a reduction in IL-4 was only significant in mice without a tumor challenge. TNF-α levels were generally reduced by the presence of the tumor itself, irrespective of the immunization status. These findings highlight a targeted immunological shift favoring anti-tumor responses.