B-cell-specific checkpoint molecules that regulate anti-tumour immunity.

The role of B cells in anti-tumour immunity is still debated and, accordingly, immunotherapies have focused on targeting T and natural killer cells to inhibit tumour growth1,2. Here, using high-throughput flow cytometry as well as bulk and single-cell RNA-sequencing and B-cell-receptor-sequencing analysis of B cells temporally during B16F10 melanoma growth, we identified a subset of B cells that expands specifically in the draining lymph node over time in tumour-bearing mice. The expanding B cell subset expresses the cell surface molecule T cell immunoglobulin and mucin domain 1 (TIM-1, encoded by Havcr1) and a unique transcriptional signature, including multiple co-inhibitory molecules such as PD-1, TIM-3, TIGIT and LAG-3. Although conditional deletion of these co-inhibitory molecules on B cells had little or no effect on tumour burden, selective deletion of Havcr1 in B cells both substantially inhibited tumour growth and enhanced effector T cell responses. Loss of TIM-1 enhanced the type 1 interferon response in B cells, which augmented B cell activation and increased antigen presentation and co-stimulation, resulting in increased expansion of tumour-specific effector T cells. Our results demonstrate that manipulation of TIM-1-expressing B cells enables engagement of the second arm of adaptive immunity to promote anti-tumour immunity and inhibit tumour growth

Impact of DOTS expansion on tuberculosis related outcomes and costs in Haiti

BACKGROUND: Implementation of the World Health Organization's DOTS strategy (Directly Observed Treatment Short-course therapy) can result in significant reduction in tuberculosis incidence. We estimated potential costs and benefits of DOTS expansion in Haiti from the government, and societal perspectives. METHODS: Using decision analysis incorporating multiple Markov processes (Markov modelling), we compared expected tuberculosis morbidity, mortality and costs in Haiti with DOTS expansion to reach all of the country, and achieve WHO benchmarks, or if the current situation did not change. Probabilities of tuberculosis related outcomes were derived from the published literature. Government health expenditures, patient and family costs were measured in direct surveys in Haiti and expressed in 2003 US$. RESULTS: Starting in 2003, DOTS expansion in Haiti is anticipated to cost$4.2 million and result in 63,080 fewer tuberculosis cases, 53,120 fewer tuberculosis deaths, and net societal savings of $131 million, over 20 years. Current government spending for tuberculosis is high, relative to the per capita income, and would be only slightly lower with DOTS. Societal savings would begin within 4 years, and would be substantial in all scenarios considered, including higher HIV seroprevalence or drug resistance, unchanged incidence following DOTS expansion, or doubling of initial and ongoing costs for DOTS expansion. CONCLUSION: A modest investment for DOTS expansion in Haiti would provide considerable humanitarian benefit by reducing tuberculosis-related morbidity, mortality and costs for patients and their families. These benefits, together with projected minimal Haitian government savings, argue strongly for donor support for DOTS expansion

Características biológicas de Boophilus microplus (acari: ixodidae) a partir de infestação experimental em cão Biological characteristics of Boophilus microplus (acari: ixodidae) on dog under experimental infestation

Boophilus microplus (Canestrini, 1887), um parasita comum dos bovinos, tem sido observado em cães. Com objetivo de descrever características biológicas desse parasitismo, um cão foi infestado experimentalmente com 10.000 larvas de B. microplus previamente mantidas em câmara climatizada a 27 ± 1 ºC e umidade relativa superior a 80%. A média da fase parasitária foi de 24,4 ± 1,50 dias, com uma taxa de recuperação de 0,42%. Das 21 fêmeas desprendidas natural e precocemente do hospedeiro, 6 (28%) ingurgitaram o suficiente (75,1 ± 30,23mg) para realizar postura. O período médio de prépostura foi de 4,33 ± 1,37 dias e o período médio de postura de 9,17 ± 2,32 dias, com produção média de 18,78 ± 15,34mg de postura. O índice médio de produção de ovos observado foi de 22,38%. Estes resultados demonstraram que fêmeas de B. microplus alimentadas em cão experimentalmente infestado, completam seu ciclo biológico. A obtenção de fêmeas, capazes de realizar posturas viáveis, sugerem a possibilidade do cão atuar como hospedeiro alternativo para B. microplus, especialmente quando não há disponível outra espécie de hospedeiro preferencial.<br>Boophilus microplus, a common parasite of cattle, has eventually reported in dogs. To describe biological features of this parasitism, one dog was experimentally infested with 10,000 larvae of B. microplus which were previously held in acclimatized camera at 27 ±1ºC and relative humidity up to 80%. The mean of parasitic phase was 24.4 ± 1.50 days, with 0.42% of recovery rate. Of 21 natural detached B. microplus females, six engorged enough (75.1 ± 30.23mg) to achieve posture. The mean period of pre-posture was 4.33 ± 1.37 days and the means period of posture was 9.17 ± 2.32, producing a mean of 18.78 ± 15.34 posture weight. The mean of eggs production index observed was 22.38%. The results showed that B. microplus females fed on dogs to complete their life cycle. The females collected were able to ovoposite viable eggs suggesting that dogs can be a possible alternative hosts to B. microplus, especially when there is no other preferential host species available