Ameliorative Effects of Tocilizumab on Lung and Liver Metastatic Lesions

Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by limited treatment options and high metastatic potential. This study investigated the anti-metastatic effects of Tocilizumab, an IL-6 receptor antagonist, alone and in combination with Cisplatin in a 4T1 murine TNBC model. Female BALB/c mice were orthotopically implanted with 4T1 cells and assigned to five groups: negative control, tumor control, Tocilizumab, Cisplatin, and combination therapy. Treatments were administered intraperitoneally over four weeks. After euthanasia, lung and liver tissues were evaluated macroscopically, histologically, and immunohistochemically to assess metastatic burden and expression levels of IL-6, NF-κB, TNF-α, and Caspase-3. Histopathological analysis revealed a significant reduction in the number and size of metastatic lesions, with the greatest suppression observed in the combination group. Immunohistochemical results showed increased Caspase-3 expression, particularly in the combination group, indicating enhanced apoptosis. IL-6 expression was elevated in Tocilizumab-treated groups, consistent with receptor blockade mechanisms. NF-κB and TNF-α levels showed variable, treatment-dependent modulation, suggesting dynamic changes in the tumor microenvironment. Overall, the findings highlight the therapeutic potential of targeting IL-6-mediated signaling in TNBC. The synergistic effect of Tocilizumab combined with Cisplatin not only suppressed metastasis but also influenced key inflammatory and apoptotic pathways. These results provide preclinical evidence supporting the integration of immunomodulatory agents with standard chemotherapy to improve outcomes in metastatic TNBC.