Evaluation of a computer-assisted multi-professional intervention to address lifestyle-related risk factors for overweight and obesity in expecting mothers and their infants: protocol for an effectiveness-implementation hybrid study.

BACKGROUND: The first 1000 days after conception are a critical period to encourage lifestyle changes to reduce the risk of childhood obesity and early programming of chronic diseases. A healthy lifestyle during pregnancy is also crucial to avoid high post-partum weight retention. Currently, lifestyle changes are not consistently discussed during routine health services in Germany. The objective of this study is to evaluate a novel computer-assisted lifestyle intervention embedded in prenatal visits and infant check-ups. The intervention seeks to reduce lifestyle-related risk factors for overweight and obesity among expecting mothers and their infants. METHODS: The study is designed as a hybrid effectiveness-implementation trial to simultaneously collect data on the effectiveness and implementation of the lifestyle intervention. The trial will take place in eight regions of the German state Baden-Wuerttemberg. Region were matched using propensity score matching. Expecting mothers (n = 1860) will be recruited before 12 weeks of gestation through gynecological practices and followed for 18 months. During 11 routine prenatal visits and infant check-ups gynecologists, midwives and pediatricians provide lifestyle counseling using Motivational Interviewing techniques. The primary outcome measure is the proportion of expecting mothers with gestational weight gain within the recommended range. To understand the process of implementation (focus group) interviews will be conducted with providers and participants of the lifestyle intervention. Additionally, an analysis of administrative data and documents will be carried out. An economic analysis will provide insights into cost and consequences compared to routine health services. DISCUSSION: Findings of this study will add to the evidence on lifestyle interventions to reduce risk for overweight and obesity commenced during pregnancy. Insights gained will contribute to the prevention of early programming of chronic disease. Study results regarding implementation fidelity, adoption, reach and cost-effectiveness of the lifestyle intervention will inform decisions about scale up and public funding. TRIAL REGISTRATION: German Clinical Trials Register (DRKS00013173). Registered 3rd of January 2019, https://www.drks.de.

Targeting myeloid cells in the tumor sustaining microenvironment.

Myeloid cells are the most abundant cells in the tumor microenvironment (TME). The tumor recruits and modulates endogenous myeloid cells to tumor-associated macrophages (TAM), dendritic cells (DC), myeloid-derived suppressor cells (MDSC) and neutrophils (TAN), to sustain an immunosuppressive environment. Pathologically overexpressed mediators produced by cancer cells like granulocyte-macrophage colony-stimulating- and vascular endothelial growth factor induce myelopoiesis in the bone marrow. Excess of myeloid cells in the blood, periphery and tumor has been associated with tumor burden. In cancer, myeloid cells are kept at an immature state of differentiation to be diverted to an immunosuppressive phenotype. Here, we review human myeloid cells in the TME and the mechanisms for sustaining the hallmarks of cancer. Simultaneously, we provide an introduction into current and novel therapeutic approaches to redirect myeloid cells from a cancer promoting to a rather inflammatory, cancer inhibiting phenotype. In addition, the role of platelets for tumor promotion is discussed.

Innate Effector-Memory T-Cell Activation Regulates Post-Thrombotic Vein Wall Inflammation and Thrombus Resolution.

RATIONALE: Immune cells play an important role during the generation and resolution of thrombosis. T cells are powerful regulators of immune and nonimmune cell function, however, their role in sterile inflammation in venous thrombosis has not been systematically examined. OBJECTIVE: This study investigated the recruitment, activation, and inflammatory activity of T cells in deep vein thrombosis and its consequences for venous thrombus resolution. METHODS AND RESULTS: CD4+ and CD8+ T cells infiltrate the thrombus and vein wall rapidly on deep vein thrombosis induction and remain in the tissue throughout the thrombus resolution. In the vein wall, recruited T cells largely consist of effector-memory T (TEM) cells. Using T-cell receptor transgenic reporter mice, we demonstrate that deep vein thrombosis-recruited TEM receive an immediate antigen-independent activation and produce IFN-γ (interferon) in situ. Mapping inflammatory conditions in the thrombotic vein, we identify a set of deep vein thrombosis upregulated cytokines and chemokines that synergize to induce antigen-independent IFN-γ production in CD4+ and CD8+ TEM cells. Reducing the number of TEM cells through a depletion recovery procedure, we show that intravenous TEM activation determines neutrophil and monocyte recruitment and delays thrombus neovascularization and resolution. Examining T-cell recruitment in human venous stasis, we show that superficial varicose veins preferentially contain activated memory T cells. CONCLUSIONS: TEM orchestrate the inflammatory response in venous thrombosis affecting thrombus resolution.

Albumin nanocapsules and nanocrystals for efficient intracellular drug release.

In order to achieve a therapeutic effect, many drugs have to reach specific cellular compartments. Nanoscale drug delivery systems extend the circulation time, reduce adverse effects and thus improve tolerability compared to systemic administration. We have developed two types of albumin-coated nanocarriers equipped with built-in dyes to track their cellular uptake and intracellular enzymatic opening. Using the approved antiprotozoal drug and STAT3 inhibitor Atovaquone (Ato) as prototype for a hydrophobic small molecule, we show that Ato-loaded ovalbumin-coated nanocapsules (Ato-nCap) preferentially enter human myeloid cells. In contrast, Ato nanocrystals coated with human serum albumin (Ato-nCry) distribute their cargo in all different immune cell types, including T and B cells. By measuring the effect of Ato nanocarriers on induced STAT3 phosphorylation in IL-10-primed human dendritic cells and constitutive STAT3 phosphorylation in human melanoma cells, we demonstrate that the intracellular Ato release is particularly effective from Ato nanocrystals and less toxic than equal doses of free drug. These new nanocarriers thus represent effective systems for intracellular drug delivery.

Transforming Health Care Delivery towards Value-Based Health Care in Germany: A Delphi Survey among Stakeholders.

Value-based healthcare (VBC) represents one strategy to meet growing challenges in healthcare systems. To date, VBC is not implemented broadly in the German healthcare system. A Delphi survey was conducted to explore stakeholders' perspectives on the relevance and feasibility of actions and practices related to the implementation of VBC in the German healthcare system. Panellists were selected using purposive sampling. Two iterative online survey rounds were conducted which were preceded by a literature search and semi-structured interviews. After two survey rounds, a consensus was reached on 95% of the items in terms of relevance and on 89% of the items regarding feasibility. The expert panels' responses were in favor of the presented actions and practices of VBC in 98% of items for which consensus was found (n = 101). Opposition was present regarding the relevance of health care being provided preferably in one location for each indication. Additionally, the panel considered inter-sectoral joint budgets contingent on treatment outcomes achieved as not feasible. When planning the next steps in moving towards a value-based healthcare system, policymakers should take into account this study's results on stakeholders' perceptions of the relative importance and feasibility of VBC components. This ensures that regulatory changes are aligned with stakeholder values, facilitating greater acceptance and more successful implementation.

Effectiveness of a Brief Lifestyle Intervention in the Prenatal Care Setting to Prevent Excessive Gestational Weight Gain and Improve Maternal and Infant Health Outcomes.

Research on perinatal programming shows that excessive gestational weight gain (GWG) increases the risk of overweight and obesity later in a child's life and contributes to maternal weight retention and elevated risks of obstetrical complications. This study examined the effectiveness of a brief lifestyle intervention in the prenatal care setting, compared to routine prenatal care, in preventing excessive GWG as well as adverse maternal and infant health outcomes. The GeMuKi study was designed as a cluster RCT using a hybrid effectiveness implementation design and was conducted in the prenatal care setting in Germany. A total of 1466 pregnant women were recruited. Pregnant women in intervention regions received up to six brief counseling sessions on lifestyle topics (e.g., physical activity, nutrition, drug use). Data on GWG and maternal and infant outcomes were entered into a digital data platform by the respective healthcare providers. The intervention resulted in a significant reduction in the proportion of women with excessive GWG (OR = 0.76, 95% CI (0.60 to 0.96), p = 0.024). Gestational weight gain in the intervention group was reduced by 1 kg (95% CI (−1.56 to −0.38), p < 0.001). No evidence of intervention effects on pregnancy, birth, or neonatal outcomes was found.

Preventive Counseling in Routine Prenatal Care-A Qualitative Study of Pregnant Women's Perspectives on a Lifestyle Intervention, Contrasted with the Experiences of Healthcare Providers.

Maternal lifestyle during pregnancy and excessive gestational weight gain can influence maternal and infant short and long-term health. As part of the GeMuKi intervention, gynecologists and midwives provide lifestyle counseling to pregnant women during routine check-up visits. This study aims to understand the needs and experiences of participating pregnant women and to what extent their perspectives correspond to the experiences of healthcare providers. Semi-structured interviews were conducted with 12 pregnant women and 13 multi-professional healthcare providers, and were analyzed using qualitative content analysis. All interviewees rated routine check-up visits as a good setting in which to focus on lifestyle topics. Women in their first pregnancies had a great need to talk about lifestyle topics. None of the participants were aware of the link between gestational weight gain and maternal and infant health. The healthcare providers interviewed attributed varying relevance regarding the issue of weight gain and, accordingly, provided inconsistent counseling. The pregnant women expressed dissatisfaction regarding the multi-professional collaboration. The results demonstrate a need for strategies to improve multi-professional collaboration. In addition, health care providers should be trained to use sensitive techniques to inform pregnant women about the link between gestational weight gain and maternal and infant health.

Understanding Determinants of Pregnant Women's Knowledge of Lifestyle-Related Risk Factors: A Cross-Sectional Study.

Research indicates that a woman's lifestyle during pregnancy influences her child's health and development. Therefore, women need to possess sufficient knowledge regarding the elements of a healthy lifestyle during pregnancy. To date, there has been little research on the assessment of lifestyle knowledge of pregnant women in the perinatal healthcare setting. This study describes the development and application of a knowledge-based questionnaire for pregnancy to be used in a lifestyle intervention trial conducted in Germany. Within the trial, pregnant women receive counselling on lifestyle topics. These topics are based on the German initiative 'Healthy Start-Young Family Network' (GiL), which provides evidence-based recommendations regarding diet and lifestyle before and during pregnancy. These serve as a basis for health professionals who provide counselling on healthy lifestyle choices during the antenatal period. The questionnaire consists of eight items, each of which can be answered using 'Yes', 'No' or 'Don't know'. The pregnant women who completed the questionnaire at baseline around the twelfth week of gestation were recruited within the host trial from gynaecological practices in Germany. Demographic variables and the respondents' answers to the questionnaire were analysed using descriptive statistics and regression analyses. Descriptive statistics show that more than 85% of participants answered the majority of questions (n = 5) correctly. Questions on whether tap water is safe and the normal range for gestational weight gain (GWG) were answered correctly by about 62% and 74% of the women, respectively, and the question on whether it is beneficial to obtain information on breastfeeding at an early stage was answered correctly by about 29%. The results of the regression analyses indicate that age, gestational week, education and income are positive predictors for answering the questionnaire correctly. Nullipara and migration background are predictors for answering the questions incorrectly. This study indicates that there are gaps in women's knowledge regarding lifestyle during pregnancy. Particular focus on certain topics, such as breastfeeding and normal GWG ranges, is still required during counselling. Our analysis shows that migration background is a predictor of insufficient knowledge and incorrect answers to the questions. Women with such backgrounds require special attention during antenatal counselling in order to cater to their needs and the gaps in their knowledge.

Health Literacy among Pregnant Women in a Lifestyle Intervention Trial.

Health literacy plays a crucial role during pregnancy, influencing the mother's health behavior which in turn affects the unborn child's health. To date, there are only few studies that report on health literacy among pregnant women or even interventions to promote health literacy. GeMuKi (acronym for "Gemeinsam Gesund: Vorsorge plus für Mutter und Kind"-Strengthening health promotion: enhanced check-up visits for mother and child) is a cluster-randomized controlled trial, aimed at improving health literacy in pregnant women by means of a lifestyle intervention in the form of brief counseling. The women in the intervention group receive counseling on lifestyle topics, such as nutrition and physical activity, during their regular prenatal check-ups. The counseling is tailored to the needs of pregnant women. Demographic data is collected at baseline using a paper-based questionnaire. Data on health literacy is collected using the Health Literacy Survey Europe with 16 items (HLS-EU-16) at baseline and the Brief Health Literacy Screener (BHLS) questionnaire at two points during the pregnancy by means of an app, which was developed specifically for the purpose of the project. The results of the study indicate that around 61.9% of the women participating in the GeMuKi study have an adequate level of health literacy at baseline. The regression analyses (general estimating equations) showed no significant effect of the GeMuKi intervention on general health literacy as measured by the BHLS (ß = 0.086, 95% CI [-0.016-0.187]). However, the intervention was significantly positively associated with pregnancy specific knowledge on lifestyle (ß = 0.089, 95% CI [0.024-0.154]). The results of this study indicate that GeMuKi was effective in improving specific pregnancy related knowledge, but did not improve general health literacy.

Health literacy among pregnant women in a lifestyle intervention trial: protocol for an explorative study on the role of health literacy in the perinatal health service setting.

INTRODUCTION: Pregnancy is a vulnerable period that affects long-term health of pregnant women and their unborn infants. Health literacy plays a crucial role in promoting healthy behaviour and thereby maintaining good health. This study explores the role of health literacy in the GeMuKi (acronym for 'Gemeinsam Gesund: Vorsorge plus für Mutter und Kind'-Strengthening health promotion: enhanced check-up visits for mother and child) Project. It will assess the ability of the GeMuKi lifestyle intervention to positively affect health literacy levels through active participation in preventive counselling. The study also explores associations between health literacy, health outcomes, health service use and effectiveness of the intervention. METHODS AND ANALYSIS: The GeMuKi trial has a hybrid effectiveness-implementation design and is carried out in routine prenatal health service settings in Germany. Women (n=1860) are recruited by their gynaecologist during routine check-up visits before 12 weeks of gestation. Trained healthcare providers carry out counselling using motivational interviewing techniques to positively affect health literacy and lifestyle-related risk factors. Healthcare providers (gynaecologists and midwives) and women jointly agree on Specific, Measurable, Achievable Reasonable, Time-Bound goals. Women will be invited to fill in questionnaires at two time points (at recruitment and 37th-40th week of gestation) using an app. Health literacy is measured using the German version of the Health Literacy Survey-16 and the Brief Health Literacy Screener. Lifestyle is measured with questions on physical activity, nutrition, alcohol and drug use. Health outcomes of both mother and child, including gestational weight gain (GWG) will be documented at each routine visit. Health service use will be assessed using social health insurance claims data. Data analyses will be conducted using IBM SPSS Statistics, version 26.0. These include descriptive statistics, tests and regression models. A mediation model will be conducted to answer the question whether health behaviour mediates the association between health literacy and GWG. ETHICS AND DISSEMINATION: The study was approved by the University Hospital of Cologne Research Ethics Committee (ID: 18-163) and the State Chamber of Physicians in Baden-Wuerttemberg (ID: B-F-2018-100). Study results will be disseminated through (poster) presentations at conferences, publications in peer-reviewed journals and press releases. TRAIL REGISTRATION: German Clinical Trials Register (DRKS00013173). Registered pre-results, 3rd of January 2019, https://www.drks.de.

Health Literacy in Pregnant Women: A Systematic Review.

Health literacy plays a crucial role during pregnancy, as the mother's health behavior influences both her own health and that of her child. To the authors' best knowledge, no comprehensive overview on evidence of the health literacy of pregnant women and its impact on health outcomes during pregnancy exists. Therefore, this review aims to assess health literacy levels in pregnant women, whether health literacy is associated with outcomes during pregnancy and whether effective interventions exist to improve the health literacy of pregnant women. A systematic literature search was conducted in PubMed and EBSCO, resulting in 14 studies. The results show mixed levels of health literacy in pregnant women. Limited health literacy is associated with unhealthy behaviors during pregnancy. Mixed health literacy levels can be attributed to the recruitment site, the number of participants and the measurement tool used. Quality assessment reveals that the quality of the included studies is moderate to good. The review revealed that randomized controlled trials and interventions to improve health literacy in pregnant women are rare or do not exist. This is crucial in the light of the mixed health literacy levels found among pregnant women. Healthcare providers play a key role in this context, as pregnant women with limited health literacy rely on them as sources of health information.

Recruitment in Health Services Research-A Study on Facilitators and Barriers for the Recruitment of Community-Based Healthcare Providers.

In health services research, the recruitment of patients is oftentimes conducted by community-based healthcare providers. Therefore, the recruitment of these healthcare providers is a crucial prerequisite for successful patient recruitment. However, recruiting community-based healthcare providers poses a major challenge and little is known about its influencing factors. This qualitative study is conducted alongside a health services research intervention trial. The aim of the study is to investigate facilitators and barriers for the recruitment of community-based healthcare providers. A qualitative text analysis of documents and semi-structured interviews with recruiting staff is performed. An inductive-deductive category-based approach is used. Our findings identify intrinsic motivation and interest in the trial's aims and goals as important facilitating factors in healthcare provider recruitment. Beyond that, extrinsic motivation generated through financial incentives or collegial obligation emerged as a conflicting strategy. While extrinsic motivation might aid in the initial enrollment of healthcare providers, it rarely resulted in active trial participation in the long run. Therefore, extrinsic motivational factors should be handled with care when recruiting healthcare providers for health services research intervention trials.

[Prospects for the implementation of the Innovation Fund project GeMuKi - a cross sectional study on attitudes of health care providers regarding preventive lifestyle counselling in routine prenatal visits and infant check-ups]. / Perspektiven für die Implementierung des Innovationsfondsprojekt GeMuKi: Eine Querschnittserhebung der Einstellungen von Leistungserbringern zu einer präventiven Lebensstilberatung in den Schwangerschafts- und Kindervorsorgeuntersuchungen.

INTRODUCTION: Overweight and obesity are major public health concerns in Germany. As patients can easily be accessed via physicians' offices, this setting provides a high potential for prevention. However, the limited implementation of prevention and health promotion interventions in physicians' offices so far indicates that barriers to implementation exist. This study therefore addresses how obesity prevention interventions should be designed and implemented so that health care providers perceive them as appropriate and are willing to adopt them in their daily practice. The study is performed by taking the Innovation Fund project "GeMuKi" as an example. METHODS: A mixed-methods study was conducted. Data collection took place within the context of the GeMuKi training session that health care providers complete in preparation for implementing the intervention. Gynecologists, pediatricians, midwives, and medical assistants completed a questionnaire. The questions covered the implementation outcomes "appropriateness" and "adoption". Text entry fields were used to obtain information on feasibility as well as anticipated facilitating and hindering factors. In addition, observation protocols were prepared for each training session by the project team. The questionnaire was analyzed descriptively. Text entry fields and protocols were evaluated using qualitative content analysis. RESULTS: Four hundred and one (n=401) training participants completed the questionnaire. Almost three quarters (73 %) of the health care providers indicate that they are motivated to implement the intervention. At the same time, concerns are expressed about organizational feasibility in everyday practice. Nevertheless, 72 % expect their care to improve as a result of the project. CONCLUSION: The health care providers surveyed are positive about the implementation of the project in everyday practice. By documenting concerns about the implementation, the barriers identified can be addressed during the project course.

Immune signature as predictive marker for response to checkpoint inhibitor immunotherapy and overall survival in melanoma.

BACKGROUND: Malignant melanoma is an immunogenic skin cancer with an increasing global incidence. Advanced stages of melanoma have poor prognoses. Currently, there are no reliable parameters to predict a patient's response to immune checkpoint inhibitor (ICI) therapy. METHODS: This study highlights the relevance of a distinct immune signature in the blood for response to ICI therapy and overall survival (OS). Therefore, the immune cell composition in the peripheral blood of 45 melanoma patients prior to ICI therapy was analyzed by flow cytometry and complete blood count. RESULTS: Responders to ICI therapy displayed an abundance of proliferating CD4+ T cells, an increased lymphocyte-to-monocyte ratio, a low platelet-to-lymphocyte ratio, low levels of CTLA-4+ Treg, and (arginase 1+ ) polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC). Nevertheless, non-responders with similar immune cell compositions also benefited from therapy displaying increased long-term OS. CONCLUSIONS: Our study demonstrated that the observed immune signature in the peripheral blood of melanoma patients prior to treatment could identify responders as well as non-responders that benefit from ICI immunotherapies.

Platelet-Derived GARP Induces Peripheral Regulatory T Cells-Potential Impact on T Cell Suppression in Patients with Melanoma-Associated Thrombocytosis.

Platelets have been recently described as an important component of the innate and adaptive immunity through their interaction with immune cells. However, information on the platelet-T cell interaction in immune-mediated diseases remains limited. Glycoprotein A repetitions predominant (GARP) expressed on platelets and on activated regulatory T cells (Treg) is involved in the regulation of peripheral immune responses by modulating the bioavailability of transforming growth factor ß (TGF-ß). Soluble GARP (sGARP) exhibits strong regulatory and anti-inflammatory capacities both in vitro and in vivo, leading to the induction of peripheral Treg. Herein, we investigated the effect of platelet-derived GARP on the differentiation, phenotype, and function of T effector cells. CD4+CD25- T cells cocultured with platelets upregulated FoxP3, the master transcription factor for Treg, were anergic, and were strongly suppressive. These effects were reversed by using a blocking anti-GARP antibody, indicating a dependency on GARP. Importantly, melanoma patients in different stages of disease showed a significant upregulation of GARP on the platelet surface, correlating to a reduced responsiveness to immunotherapy. In conclusion, our data indicate that platelets induce peripheral Treg via GARP. These findings might contribute to diseases such as cancer-associated thrombocytosis, wherein poor prognosis and metastasis are associated with high counts of circulating platelets.

Influence of the initial level of consciousness on early, goal-directed mobilization: a post hoc analysis.

PURPOSE: Early mobilization within 72 h of intensive care unit (ICU) admission improves functional status at hospital discharge. We aimed to assess the effectiveness of early, goal-directed mobilization in critically ill patients across a broad spectrum of initial consciousness levels. METHODS: Post hoc analysis of the international, randomized, controlled, outcome-assessor blinded SOMS trial conducted 2011-2015. Randomization was stratified according to the immediate post-injury Glasgow Coma Scale (GCS) (≤ 8 or > 8). Patients received either SOMS-guided mobility treatment with a facilitator or standard care. We used general linear models to test the hypothesis that immediate post-randomization GCS modulates the intervention effects on functional independence at hospital discharge. RESULTS: Two hundred patients were included in the intention-to-treat analysis. The significant effect of early, goal-directed mobilization was consistent across levels of GCS without evidence of effect modification, for the primary outcome functional independence at hospital discharge (p = 0.53 for interaction), as well as average achieved mobility level during ICU stay (mean achieved SOMS level) and functional status at hospital discharge measured with the functional independence measure. In patients with low GCS, delay to first mobilization therapy was longer (0.7 ± 0.2 days vs. 0.2 ± 0.1 days, p = 0.008), but early, goal-directed mobilization compared with standard care significantly increased functional independence at hospital discharge in this subgroup of patients with immediate post-randomization GCS ≤ 8 (OR 3.67; 95% CI 1.02-13.14; p = 0.046). CONCLUSION: This post hoc analysis of a randomized controlled trial suggests that early, goal-directed mobilization in patients with an impaired initial conscious state (GCS ≤ 8) is not harmful but effective.

BRAF inhibitors stimulate inflammasome activation and interleukin 1 beta production in dendritic cells.

Melanoma is the most dangerous form of skin cancer with a growing incidence over the last decades. Fourty percent of all melanomas harbor a mutation in the signaling adaptor BRAF (V600E) that results in ERK hyperactivity as an oncogenic driver. In these cases, treatment with the BRAFV600E inhibitors Vemurafenib (VEM) or Dabrafenib (DAB) coapplied with the MEK1/2 inhibitors Cobimetinib (COB) or Trametinib (TRA) can result in long-term suppression of tumor growth. Besides direct suppression of ERK activity, these inhibitors have been reported to also modulate tumor immune responses, and exert pro-inflammatory side effects such as fever and rash in some patients. Here we asked for potential effects of BRAFV600E inhibitors on dendritic cells (DC) which are essential for the induction of adaptive anti-tumor responses. Both splenic and bone marrow-derived (BM) mouse dendritic cells (DC) up-regulated costimulator expression (CD80, CD86) in response to DAB but not VEM treatment. Moreover, DAB and to lesser extent VEM enhanced IL-1ß (interleukin 1 beta) release by splenic DC, and by LPS-stimulated BMDC. We demonstrate that DAB and VEM activated the NLRC4/Caspase-1 inflammasome. At high concentration, DAB also induced inflammasome activation independent of Caspase-1. TRA and COB elevated MHCII expression on BMDC, and modulated the LPS-induced cytokine pattern. Immunomodulatory activity of DAB and VEM was also observed in human monocyte-derived DC, and DAB induced IL-1ß in human primary DC. Altogether, our study shows that BRAFV600E inhibitors upregulate IL-1ß release by mouse and human DC which may affect the DC-mediated course of anti-tumor immune responses.