Blocking IL-1ß reverses the immunosuppression in mouse breast cancer and synergizes with anti-PD-1 for tumor abrogation.

Interleukin-1ß (IL-1ß) is abundant in the tumor microenvironment, where this cytokine can promote tumor growth, but also antitumor activities. We studied IL-1ß during early tumor progression using a model of orthotopically introduced 4T1 breast cancer cells. Whereas there is tumor progression and spontaneous metastasis in wild-type (WT) mice, in IL-1ß-deficient mice, tumors begin to grow but subsequently regress. This change is due to recruitment and differentiation of inflammatory monocytes in the tumor microenvironment. In WT mice, macrophages heavily infiltrate tumors, but in IL-1ß-deficient mice, low levels of the chemokine CCL2 hamper recruitment of monocytes and, together with low levels of colony-stimulating factor-1 (CSF-1), inhibit their differentiation into macrophages. The low levels of macrophages in IL-1ß-deficient mice result in a relatively high percentage of CD11b+ dendritic cells (DCs) in the tumors. In WT mice, IL-10 secretion from macrophages is dominant and induces immunosuppression and tumor progression; in contrast, in IL-1ß-deficient mice, IL-12 secretion by CD11b+ DCs prevails and supports antitumor immunity. The antitumor immunity in IL-1ß-deficient mice includes activated CD8+ lymphocytes expressing IFN-γ, TNF-α, and granzyme B; these cells infiltrate tumors and induce regression. WT mice with 4T1 tumors were treated with either anti-IL-1ß or anti-PD-1 Abs, each of which resulted in partial growth inhibition. However, treating mice first with anti-IL-1ß Abs followed by anti-PD-1 Abs completely abrogated tumor progression. These data define microenvironmental IL-1ß as a master cytokine in tumor progression. In addition to reducing tumor progression, blocking IL-1ß facilitates checkpoint inhibition.

Disparities in Effectiveness of Pneumococcal Vaccine in Industrialized and Developing Countries: Is Vaccination Closing the Gap?.

Background Streptococcus pneumoniae cause serious disease including pneumonia, meningitis and bacteremia and mortality.is seen most in developing countries. The aim of the study was to determine if the reduction in IPD aid pneumonia rates were similar in developed and developing countries after the introduction of the pneumococcal conjugated vaccine and to determine changes in the disparities of these diseases rates in these countries. METHODS: Literature searches were conducted by using the PubMed database and Google scholar. The main criterion for selection was,that the studies compare incidence of IPD or pneumonia in children pre and post PCV7, PCV10, or PCV13 vaccine introduction. Only published articles that described the incidence rate of IPD or pneumonia with quantitative data were fully reviewed in detail. RESULTS: A total of 22 articles were full-text original publications and one was a review article. Within 3 years of PCV introduction in the United States, all-cause IPD dropped from 98.7/100,000 to 20/100,000 children <5 years of age and similar such reductions were also documented in Europe, Canada, Australia and Israel. In South Africa, rate of IPD incidence among children younger than 2 years of age declined from 54.8 to 21.7 cases per 100,000 from the baseline to 2011 and the further decreased to 17.0 cases per 100,000 person in 2012 (total reduction of 69%. The incidence rates of pneumonia in chil- dren <5 years were estimated to be 0.29,episodes per child-year in developing-and 0.05 episodes per child-year in developed countries. After PCV7 introduction the rates of pneumonia hospitalizations in <5 years old decreased in the US from 1,274/100,000 to 723/100,000 in UK, from 1,340/100,000 children to 1,079/per 100,000 children. In Nicaragua reduction of rate ration of 0.67 (95% CI: 0.59-0.75) among infants and 0.74 (95% CI: 0.67-0.81) among 1 year olds and Uruguay from 1,542/100,000 to 1,227/100,000 -and in South Africa, from -96/1,000 in 2008-2009 to 69.3/1,000 (27.8%). CONCLUSIONS: PCVs are effective in both industrialized and developing countries in reducing IPD and pneumonia. Although developing countries are behind in PCV introduction, there is hope that if PCV is introduced in national immunization programs, IPD can perhaps be reduced to that of levels in industrialized countries, also resulting in reduced levels of pneumonia incidences. More surveillance studies are needed in all countries, but especially in developing countries that have introduced PCV to more accurately determine IPD and pneumonia reduction as a result of vaccination.

A rapid postmortem screening test for lead toxicosis in common loons (Gavia immer) and bald eagles (Haliaeetus leucocephalus).

In live animals, lead poisoning can be diagnosed by analyzing blood samples. For postmortem testing, blood samples are not available and analysis of liver or kidney is often used for diagnosis. Liver and kidney analysis is relatively expensive and results might not be quickly available. We examined an inexpensive, rapid method to screen animals for lead toxicosis postmortem by testing the mixture of body fluids (termed "tissue fluids") that pool in the body cavity at necropsy for lead. At necropsy we collected body fluid and liver samples from Common Loon (Gavia immer) and Bald Eagle (Haliaeetus leucocephalus) carcasses and determined concentrations of lead in tissue fluid using a desk-top blood lead analyzer. Concentrations of lead in liver were determined by inductively coupled plasma mass spectroscopy. There was strong correlation between tissue fluid and liver tissue lead concentrations, and receiver-operating characteristic analysis gave an area under the curve of 0.91, indicating that postmortem measurements of lead in tissue fluids can be utilized as a screening method for lead toxicosis.