In this study, we sought to investigate the potential application of γδ T cell-derived extracellular vesicles (γδTDEs) as drug delivery system (DDS) for miR-138 in the treatment of oral squamous cell carcinoma (OSCC). Our data showed that overexpression of miR-138 in γδ T cells obtained miR-138-rich γδTDEs accompanying increased expansion and cytotoxicity of γδ T cells. γδTDEs inherited the cytotoxic profile of γδ T cells and could efficiently deliver miR-138 to OSCC cells, resulting in synergetic inhibition on OSCC both in vitro and in vivo. The pre-immunization by miR-138-rich γδTDEs inhibited the growth of OSCC tumors in immunocompetent C3H mice, but not in nude mice, suggesting an immunomodulatory role by miR-13-rich γδTDEs. γδTDEs and miR-138 additively increased the proliferation, interferon-γ (IFN-γ) production, and cytotoxicity of CD8+ T cells against OSCC cells. Only delivered by γδTDEs can miR-138 efficiently target programmed cell death 1 (PD-1) and CTLA-4 in CD8+ T cells. We conclude that γδTDEs delivering miR-138 could achieve synergetic therapeutic effects on OSCC, which is benefited from the individual direct anti-tumoral effects on OSCC and immunostimulatory effects on T cells by both γδTDEs and miR-138; γδTDEs could serve as an efficient DDS for microRNAs (miRNAs) in the treatment of cancer.
Background Multiple studies have compared the efficacy of entecavir with lamivudine in preventing hepatitis B virus (HBV) reactivation among HBV-carrying lymphoma patients with chemotherapy treatment. However, the results were slightly varied. Aim of the review to combine the findings of independent studies assessing the clinical efficacy of the two drugs using a systematic review and meta-analysis. Methods PubMed, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Chongqing VIP and WanFang Data were retrieved. Two independent reviewers evaluated the study eligibility and extracted eight studies, with 770 patients in total. The meta-analysis was conducted using RevMan 5.3 and STATA software. Results HBV-carrying lymphoma patients receiving lamivudine during chemotherapy had a statistically significantly higher odds of HBV reactivation compared to those receiving entecavir (OR 5.0, 95 % CI 2.85-8.78, P < 0.001). The odds of hepatitis, HBV-Reactivation caused hepatitis and chemotherapy disruption was statistically significantly elevated in the patient group receiving lamivudine compared to the entecavir group (OR 4.12, 95 % CI 1.70-9.98, P = 0.002; OR 11.44, 95 % CI 2.70-48.52, P < 0.001; OR 6.71, 95 % CI 2.34-19.26, P < 0.001, respectively). Furthermore, the HBV reactivation rate in Ann Arbor stages I - II patient group was statistically significantly lower than the one in Ann Arbor stages III-IV group, with an overall pooled value of 0.37 (95 % CI 0.17-0.82, P = 0.01). Conclusion The metaanalysis result suggested that among HBV-carrying lymphoma patients undergoing chemotherapy, entecavir is more effective than lamivudine in preventing HBV reactivation.
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