Periodontitis and the link with heart disease: can common oral bacteria b e eliminated to prevent heart disease?

The importance of oral health on systemic health is a highly researched area of study in recent years. There has been a shift in dental visits from acute emergencies to ongoing preventative care due to the knowledge connecting oral and systemic health. One of the commonly researched connections is the link between periodontal disease and heart disease. Periodontal disease is defined as inflammation of the gum tissue, resulting in periodontal pockets that can lead to infection, bone loss and even loss of the tooth. Cardiovascular disease, or heart disease, is a term that encompasses many different conditions of the heart, including heart failure, myocardial infarction, atherosclerosis and angina. There is constant research to better understand the relationship between the two diseases, as well as any causality that may exist. Recent studies have been able to link the diseases, but no causal link has been found. The role of the bacteria involved in both diseases has recently been considered to see if these organisms are related to a potential causal link. Two particular bacteria that are known to be involved with periodontal disease are Porphyromona gingivalis and Treponema denticola. These bacteria are present when a patient develops periodontal disease, but they are not usually present in a healthy individual. Additionally, the bacteria that make up the contents of plaque found in the heart have been studied to see if there are any similarities with oral microbes. It has been found that oral bacteria can be present in arterial plaque samples. This research may allow a better understanding of how and why heart disease occurs and potentially serve as a way to treat heart disease accompanied by periodontal disease, if a causal relationship is elucidated. Heart disease is usually a devastating disease, sometimes resulting in the death of the patient. If more patients attend the dentist as a preventative measure, the risk of periodontal disease and associated pathologies may be reduced. Additionally, those that have already developed periodontal disease can work with a dental professional to reverse the disease. It is known that the bacteria in the mouth can enter the bloodstream upon infection, so patients with suspected periodontitis should be treated to avoid the bacteria from entering the blood and affecting other organs such as the heart. An examination of the bacteria commonly found in the oral cavity at times of periodontal disease may lead to a better understanding of how and why these bacteria invade the bloodstream. It would be beneficial to compare the microbiota of both the plaque in the mouth and the plaque in a vessel supplying the heart in a patient suffers from heart disease. This understanding may lead to therapeutic interventions that aid in the prevention of bacteria traveling in the bloodstream. For many Americans, oral health care was believed to end at home by brushing and flossing. However, it is important to see a dental professional to avoid any possible complications that may not be apparent to the untrained eye. A simple dental cleaning may be important to detect the start of periodontal disease, and treatment can be initiated to end the potential spread of bacteria. It is important to maintain positive oral health in order to maintain overall systemic health, including the avoidance of heart disease

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival