Current work is one of our comprehensive preclinical studies, a new approach to breast cancer (BC) immunotherapy through induction of tumour cell apoptosis. Tumour growth is not just a result of uncontrolled cell proliferation but also of reduced apoptosis. High levels of interleukin-6 (IL-6) are associated with metastatic BC and correlated with poor survival as it promotes growth of tumour-initiating cells during early tumorigenesis protecting these cells from apoptosis. Therefore, this study aims at investigating the potential of anti-IL-6 monoclonal antibodies to suppress IL-6 proliferative/anti-apoptotic activities in intact tumour microenvironment of BC. Fresh sterile tumour and normal breast tissue specimens were taken from 50 female Egyptian patients with BC undergoing radical mastectomy. A unique tissue culture system designed to provide cells of each intact tumour/normal tissue sample with its proper microenvironment either supplemented or not with anti-IL-6 monoclonal antibodies. To evaluate the apoptotic activity of anti-IL-6 as a novel candidate for BC treatment strategy, we compared its effects with those obtained using tumour necrosis-related apoptosis-inducing ligand TRAIL as an established apoptotic agent. Our results revealed that levels of either anti-IL-6-or TRAIL-induced apoptosis in the tumour or normal tissue cultures were significantly higher than those in their corresponding untreated ones (P < 0.001). No statistically significant differences have been found between apoptosis levels induced by anti-IL-6 monoclonal antibodies and those induced by TRAIL. Recombinant anti-IL-6 monoclonal antibodies could represent a novel effective element of immunotherapeutic treatment strategy for BC. The selectivity and anti-apoptotic potential of anti-IL-6 is highly hopeful in IL-6-abundant BC tumour microenvironment.

Background: Accumulation of myeloid-derived suppressor cells (MDSCs) constitutes a key mechanism of tumor immune evasion in gastric cancer (GC). Therefore, searching for more accurate prognostic factors affecting their immunosuppressive role has become a growing interest in cancer immunotherapy research. Increased expression of microRNA-494 was noticed in MDSCs from tumor-bearing mice, suggesting another new therapeutic objective for cancer treatment. It was also discovered that tumor-derived transforming growth factor beta (TGF-β) is responsible for the up-regulation of microRNA-494 in MDSCs. The purpose of this study was to address the effect of recombinant (rTGF-β) on the anti-inflammatory activity of MDSCs in GC and its possible association with micro-RNA-494 expression in tumor tissue. Methods: Freshly obtained GC tumor tissue samples and peripheral blood were used for isolation of CD33+11b+HLADR-MDSCs cells from 40 GC patients and 31 corresponding controls using flow cytometry. MDSCs were co-cultured with isolated autologous T cells to assess proliferation and cytokine production in the presence and absence of rTGF-β. Real-time PCR and Enzyme linked immunosorbent assay were used to evaluate tumor expression of miRNA-494 and TGF-β respectively. Results: Results showed that rTGF-β markedly increased the suppressive ability of tumor MDSCs on proliferation of autologous T cells and interferon gamma production. However, no inhibitory effect was observed for MDSCs from circulation. In addition, infiltration of MDSCs in tumors is associated with the prognosis of GC. MiRNA-494 was also extensively expressed in tumor samples with a significant correlation to MDSCs. Conclusion: These results indicate that tumor-derived MDSCs but not circulatory MDSCs have an immunosuppressive effect on T cells, potentially involving TGF-β mediated stimulation. Results also suggest a role for miRNA-494 in GC progression. Therefore, control of TGF-β and miRNA-494 may be used as a treatment strategy to downregulate the immunosuppressive effect of MDSCs.

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