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Investigating the Role of Anti-Leukemia Inhibitory Factor Antibody on Cytokine Profile in a Mouse Model of Breast
Seyed Mohammad Seifati1, Hossein Hadinedoushan1, Hossein Ansariniya1,2
1Reproductive Immunology Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Background:
Leukemia inhibitory factor (LIF), a member of the IL-6 cytokine family, is increasingly recognized as a tumor-promoting factor in breast cancer, where it contributes to immune suppression, tumor progression, and therapy resistance. While neutralizing LIF is an attractive therapeutic approach, little is known about the systemic immunological consequences of targeting this cytokine. AIMSَ: This study aimed to evaluate the effects of active immunization against recombinant LIF protein-designed to elicit endogenous anti-LIF antibodies-on tumor progression and systemic cytokine responses in a murine breast cancer model.
Methods And Results:
Female BALB/c mice were immunized with recombinant LIF protein emulsified in Freund's adjuvant to induce anti-LIF antibodies. Tumors were subsequently established by subcutaneous injection of 4T1 breast cancer cells after antibody titers were confirmed. Serum cytokine levels (IFN-γ, TNF-α, IL-6, IL-10, IL-4, and TGF-β) were measured by ELISA, and tumor growth was monitored. Active immunization against LIF significantly inhibited tumor growth compared to controls. Serum analysis revealed that anti-LIF immunization systemically suppressed tumor-induced IL-10 while significantly enhancing IFN-γ levels in tumor-bearing mice. In contrast, IL-4 reduction was only significant in the absence of tumor challenge, and TNF-α levels were generally reduced by the presence of the tumor regardless of immunization.
Conclusion:
Our findings suggest that vaccination against LIF can induce endogenous anti-LIF antibody responses, limit tumor progression, and selectively modulate systemic cytokine profiles, particularly through suppression of tumor-induced IL-10 together with enhanced IFN-γ responses in tumor-bearing mice. These findings support further investigation of LIF-targeted immunization as a potential immunotherapeutic strategy in breast cancer.
