We found that the cancerous pancreas harbors a markedly more abundant microbiome compared with normal pancreas in both mice and humans, and select bacteria are differentially increased in the tumorous pancreas compared with gut. Ablation of the microbiome protects against preinvasive and invasive pancreatic ductal adenocarcinoma (PDA), whereas transfer of bacteria from PDA-bearing hosts, but not controls, reverses tumor protection. Bacterial ablation was associated with immunogenic reprogramming of the PDA tumor microenvironment, including a reduction in myeloid-derived suppressor cells and an increase in M1 macrophage differentiation, promoting TH1 differentiation of CD4⁺ T cells and CD8⁺ T-cell activation. Bacterial ablation also enabled efficacy for checkpoint-targeted immunotherapy by upregulating PD-1 expression. Mechanistically, the PDA microbiome generated a tolerogenic immune program by differentially activating select Toll-like receptors in monocytic cells. These data suggest that endogenous microbiota promote the crippling immune-suppression characteristic of PDA and that the microbiome has potential as a therapeutic target in the modulation of disease progression. SIGNIFICANCE: We found that a distinct and abundant microbiome drives suppressive monocytic cellular differentiation in pancreatic cancer via selective Toll-like receptor ligation leading to T-cell anergy. Targeting the microbiome protects against oncogenesis, reverses intratumoral immune tolerance, and enables efficacy for checkpoint-based immunotherapy. These data have implications for understanding immune suppression in pancreatic cancer and its reversal in the clinic. Cancer Discov; 8(4);1–14. ©2018 AACR.

Background: Bacterial infections have been linked to malignancies due to their ability to induce chronic inflammation. We investigated the association of oral bacteria in oral squamous cell carcinoma (OSCC/tumor) tissues and compared with adjacent non-tumor mucosa sampled 5 cm distant from the same patient (n = 10). By using culture-independent 16S rRNA approaches, denaturing gradient gel electrophoresis (DGGE) and cloning and sequencing, we assessed the total bacterial diversity in these clinical samples. Results: DGGE fingerprints showed variations in the band intensity profiles within non-tumor and tumor tissues of the same patient and among the two groups. The clonal analysis indicated that from a total of 1200 sequences characterized, 80 bacterial species/phylotypes were detected representing six phyla, Firmicutes, Bacteroidetes, Proteobacteria, Fusobacteria, Actinobacteria and uncultivated TM7 in non-tumor and tumor libraries. In combined library, 12 classes, 16 order, 26 families and 40 genera were observed. Bacterial species, Streptococcus sp. oral taxon 058, Peptostreptococcus stomatis, Streptococcus salivarius, Streptococcus gordonii, Gemella haemolysans, Gemella morbillorum, Johnsonella ignava and Streptococcus parasanguinis I were highly associated with tumor site where as Granulicatella adiacens was prevalent at non-tumor site. Streptococcus intermedius was present in 70% of both non-tumor and tumor sites. Conclusions: The underlying changes in the bacterial diversity in the oral mucosal tissues from non-tumor and tumor sites of OSCC subjects indicated a shift in bacterial colonization. These most prevalent or unique bacterial species/phylotypes present in tumor tissues may be associated with OSCC and needs to be further investigated with a larger sample size.

Background: Many researchers claim electronic cigarettes (e-cigarettes) to be a breakthrough invention for tobacco users that aspires to curb their addiction to conventional cigarettes. Claimed to be safer by their promoters, these smokeless devices have become increasingly popular since their arrival on the market among users of all ages, especially adolescents. This paper investigated the trends in e-cigarette usage since the time it arrived in the United States, highlighting the highest surge that has occurred in adolescent e-cigarette use. It also aimed to understand the reasons and perceptions behind the ever-increasing use of e-cigarettes by adolescents. Main body: With the advent of e-cigarettes and common positive perceptions regarding their use, we are at risk of reversing the years of efforts regarding tobacco control and instead advance towards a new addiction with currently unknown long-term health hazards. There is substantial data showing a significant increase of e-cigarette users in the United States, especially among adolescents. The aim of this review was to explore the reasons behind this widespread increase in the use of e-cigarettes among the teenage population in the US and also to uncover the common perceptions about these new electronic delivery systems. In addition, this review attempted to summarize health benefits and hazards associated with e-cigarette use as it crucial to have the right information among its users regarding the health effects of e-cigarette use. Conclusion: E-cigarettes are more appealing than c-cigarettes for a variety of reasons, including cost, choice of different flavors, ease of accessibility, and use and impact of social media. There are also different perceptions among e-cigarette users, including both adolescents and adults. The former group may use them because of the sense of fashion associated with this novel device, and the latter might intend to quit conventional/combustible cigarettes (c-cigarettes) by switching to e-cigarettes. However, it is important to note that e-cigarettes are a recent phenomenon; therefore, there is a lack of many long-term studies that can identify future health risks associated with e-cigarette use. We need more detailed studies that focus on the long-term health effects of e-cigarette use. Moreover, with the ever-increasing usage of e-cigarettes by adolescents (10 and 19 years), it is very important that e-cigarettes be incorporated into the current tobacco-free laws and ordinances. We conclude by stating that e-cigarettes need stronger regulations to prevent youth access and use.

In the oral cavity, chronic inflammation has been observed at various stages of oral squamous cell carcinomas (OSCC). Such inflammation could result

The trend of e-cigarette use among teens is ever increasing. Here we show the dysbiotic oral microbial ecology in e-cigarette users influencing the local host immune environment compared with non-smoker controls and cigarette smokers. Using 16S rRNA high-throughput sequencing, we evaluated 119 human participants, 40 in each of the three cohorts, and found significantly altered beta-diversity in e-cigarette users (p = 0.006) when compared with never smokers or tobacco cigarette smokers. The abundance of Porphyromonas and Veillonella (p = 0.008) was higher among vapers. Interleukin (IL)-6 and IL-1β were highly elevated in e-cigarette users when compared with non-users. Epithelial cell-exposed e-cigarette aerosols were more susceptible for infection. In vitro infection model of premalignant Leuk-1 and malignant cell lines exposed to e-cigarette aerosol and challenged by Porphyromonas gingivalis and Fusobacterium nucleatum resulted in elevated inflammatory response. Our findings for the first time demonstrate that e-cigarette users are more prone to infection.