Macrophages have an affinity to developing tumors and have been shown to play a role in tumor combat and immune surveillance. However, the exact mechanism by which macrophages participate in the anti-tumor immune response remains unclear. Hence, the current study aimed to identify the effect of macrophages on gastric cancer (GC) cells via exosomes. Paired cancerous, tumor-adjacent, and non-cancerous stomach tissues were initially from 68 GC patients. T cells were isolated from peripheral blood mononuclear cells (PBMCs) obtained from both the GC patients as well as the healthy donors. Next, the exosomes were isolated from LPS and IFN-γ-induced PBMCs (M1 macrophages) and co-cultured with human GC cells. Another co-culture system comprised of CD3+ T cells and exosomes-treated GC cells was then performed. BALB/c mice and NOD/SCID nude mice were prepared for effects of exosomal miR-16-5p on tumor growth and anti-tumor immune response in GC in vivo. A relationship between M1 macrophages and the poor survival of GC patients was identified, while they secreted exosomes to inhibit GC development and activate a T cell-dependent immune response. Our results revealed that miR-16-5p was transferred intercellularly from M1 macrophages to GC cells via exosomes and targeted PD-L1. M1 macrophage-derived exosomes containing miR-16-5p were found to trigger a T cell immune response which inhibited tumor formation both in vitro and in vivo by decreasing the expression of PD-L1. Taken together, the key findings of the current study suggest that M1 macrophage-derived exosomes carrying miR-16-5p exert an inhibitory effect on GC progression through activation of T cell immune response via PD-L1. Our study highlights the promise of M1 macrophages as a potential cell-based therapy for GC treatment by increasing miR-16-5p in exosomes.
Background The World Health Organization (WHO) introduced the MPOWER package to support policy implementation under the Framework Convention on Tobacco Control (FCTC). This study examined the effect of MPOWER policies on smoking prevalence and cigarette consumption in a global context. Methods The MPOWER composite score was constructed by adding up the six MPOWER scores for each country and survey year 2007–2008, 2010, 2012, and 2014, with a possible range between 6 (1 in each of the six score) and 29 (4 in M score and 5 in POWER scores). MPOWER composite scores that measured policy implementation were then linked to cigarette smoking prevalence and consumption data from Euromonitor International. Fractional logit and OLS regressions were employed to examine the effect of the composite MPOWER score on adult smoking prevalence and cigarette consumption, respectively. Results Results indicate that a 1-unit increase in the composite score reduces smoking prevalence by 0.2 percentage points (p<0.05) among adults and 0.3 percentage points (p<0.01) among adult males; and a reduction of 23 sticks of cigarette (1 pack of cigarettes) in cigarette consumption per capita per year. At this rate, if countries had implemented the MPOWER package to the highest levels during 2007–2014, they would have experienced a reduction in smoking prevalence of 7.26 % among adults and 7.87% among adult males and a reduction of 13.80% in cigarette consumption. Conclusions MPOWER policies were effective in reducing cigarette smoking among adults. Parties should continue to implement MPOWER policies that have been recommended by the WHO FCTC to curb tobacco epidemic.
Background The distribution of cigarette prices has rarely been studied and compared under different tax structures. Descriptive evidence on price distributions by countries can shed light on opportunities for tax avoidance and brand switching under different tobacco tax structures, which could impact the effectiveness of increased taxation in reducing smoking. Objective This paper aims to describe the distribution of cigarette prices by countries and to compare these distributions based on the tobacco tax structure in these countries. Methods We employed data for 16 countries taken from the International Tobacco Control Policy Evaluation Project to construct survey-derived cigarette prices for each country. Self-reported prices were weighted by cigarette consumption and described using a comprehensive set of statistics. We then compared these statistics for cigarette prices under different tax structures. In particular, countries of similar income levels and countries that impose similar total excise taxes using different tax structures were paired and compared in mean and variance using a two-sample comparison test. Findings Our investigation illustrates that, compared with specific uniform taxation, other tax structures, such as ad valorem uniform taxation, mixed (a tax system using ad valorem and specific taxes) uniform taxation, and tiered tax structures of specific, ad valorem and mixed taxation tend to have price distributions with greater variability. Countries that rely heavily on ad valorem and tiered taxes also tend to have greater price variability around the median. Among mixed taxation systems, countries that rely more heavily on the ad valorem component tend to have greater price variability than countries that rely more heavily on the specific component. In countries with tiered tax systems, cigarette prices are skewed more towards lower prices than are prices under uniform tax systems. The analyses presented here demonstrate that more opportunities exist for tax avoidance and brand switching when the tax structure departs from a uniform specific tax.
The tax increases that were implemented during 2009-2015 were not enough to increase tobacco product prices sufficiently to outweigh the effect of income growth, and to reduce tobacco consumption. The findings from this research inform policymakers that in countries experiencing rapid economic growth, significant tax increases are needed to counteract the effect of income growth, in order for the tax increases to be effective in reducing tobacco use.
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