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  • The present findings showed that vaccination with CSC

    2019-10-15

    The present findings showed that vaccination with CSC-loaded DC combined with repeated cycles of low doses of cisplatin resulted in a significant inhibition of tumor growth compared with untreated control group as well as all other treated groups. These findings were supported by the work of Lu et al. (2015). Furthermore, vaccination with loaded DC either alone or in combination with cisplatin prolonged the survival of tumor bearing mice as demonstrated by our findings. These data indicate that co-treatment with CSC loaded DC and cisplatin resulted in enhanced anti-tumor outcomes compared to single treatment with ei-ther chemotherapy or loaded DCs as indicated by inhibition of sub-cutaneous tumor growth and prolonged survival of SEC bearing mice which were in line with the study of Hu et al. (2016). In the present study, we examined the ability of CSC-DC vaccine to induce cellular immune responses via induction of significant IFN- γ production. A significant increase in IFN- γ serum levels was observed in DC + chemo, Vacc, and Vacc + chemo groups as compared to un-treated control, DC, and chemo groups. Interestingly, the combination of CSC-loaded DC and cisplatin significantly augmented the antitumor immune response of cisplatin as evidenced by the significant increase in IFN- γ serum levels as compared to either single treatment with CSC- 
    loaded DC or combined treatment with unloaded DC and cisplatin. The higher IFN- γ serum levels in the Vacc + chemo group is consistent with the higher survival rate and reduction of tumor volume observed in the same group as reported by previous studies (Yu et al., 2003; Xu et al., 2009).
    Dendritic Fluxametamide
    must present tumor antigens, express co-stimulatory signals, and produce inflammatory mediators such as IFNs in order to activate naïve T cells into a functional state (Mac Keon et al., 2015). IFN-γ produced by immune cells affects other distinct immune cells within the tumor microenvironment. It plays a major role in activating anticancer immunity by promoting the activity of T-cells, NK cells, and DCs. Moreover, it was reported that IFN-γ inhibits regulatory T (Treg) cells, suggesting that IFN-γ plays an important role in tumor cell elimination (Ni and Lu, 2018).
    Wang and his co-workers showed that plasma IFN-γ levels were significantly decreased in lung cancer patients (Wang et al., 2013). It was reported by Higgs et al. that increased IFN-γ is correlated with higher response and longer survival in patients with non-small cell lung carcinoma or urothelial cancerwhich is in line with our findings (Higgs et al., 2018).
    In addition to the direct activation of specific antitumor immune response, recent approaches are directed toward combining DC-based vaccines with agents that modulate the tumor microenvironment such as chemotherapy to improve the immunogenicity and overcome the immunosuppression within the tumor microenvironment (Huber et al., 2018).
    Previous studies have shown that p53 mutation/inactivation pro-mote tumorigenesis either directly or indirectly which in turn induce tumor pro-inflammatory responses and acts as a driver of tumorigenesis through changing the immunological tumor microenvironment leading to immunosuppression. On contrary, the activation/reactivation of p53 expression contribute in reversing the immunosuppression and enhan-cing antitumor immunity (Ventura et al., 2007; Menendez et al., 2013; Cui and Guo, 2016; Guo et al., 2017). In this context, we examined the relative gene expression of p53 in tumor bearing mice which plays a significant role in the inhibition of tumor cell proliferation and induc-tion of apoptosis (Bassiony et al., 2014).
    Our results illustrated that Vacc + chemo combined treatment showed a more profound significant increase (P < 0.001) in p53 re-lative gene expression levels in comparison to its levels in other treated groups. The present findings were in accordance with previous study which illustrated that enhanced p53 expression directs the tumor cells to induce apoptosis of Ehrlich solid carcinoma cells thus inhibiting tu-morigenesis (Bassiony et al., 2014).