Dendritic cells and macrophages are common components of the tumour immune microenvironment and can contribute to immune suppression in both solid and haematological cancers. The Bone Morphogenetic Protein (BMP) pathway has been reported to be involved in cancer, and more recently in leukaemia development and progression. In the present study, we analyse whether acute lymphoblastic leukaemia (ALL) cells can affect the differentiation of dendritic cells and macrophages and the involvement of BMP pathway in the process. We show that ALL cells produce BMP4 and that conditioned media from ALL cells promote the generation of dendritic cells with immunosuppressive features and skew M1-like macrophage polarization towards a less pro-inflammatory phenotype. Likewise, BMP4 overexpression in ALL cells potentiates their ability to induce immunosuppressive dendritic cells and favours the generation of M2-like macrophages with pro-tumoral features. These results suggest that BMP4 is in part responsible for the alterations in dendritic cell and macrophage differentiation produced by ALL cells.

https://www.mdpi.com/2073-4409/8/7/722/pdf

Acute Lymphoblastic Leukaemia Cells Impair Dendritic Cell and Macrophage Differentiation: Role of BMP4

Over the last 50 years, liver transplantation has evolved into a procedure routinely performed in many countries worldwide. Those able to access this therapy frequently experience a miraculous risk-benefit ratio since, particularly if they face imminently life threatening disease. Over the decades, the success of liver transplantation, with dramatic improvements in early post-transplant survival, has aggressively driven demand. However, in spite of the emergence of living donors to augment deceased donors as a source of organs, supply has lagged far behind demand. As a result, rationing has been an unfortunate focus in recent decades. Recent shifts in the epidemiology of liver disease combined with transformative innovations in liver preservation suggest that the underlying premise of organ shortage may erode in the foreseeable future. Focus will sharpen on improving equitable access while mitigating constraints related to workforce training, infrastructure for organ recovery and rehabilitation, and their associated costs. Research efforts in liver preservation will undoubtedly blossom with the aim of optimizing both the timing and conditions of transplantation. Coupled with advances in genetic engineering, regenerative biology, and cellular therapies, the portfolio of innovation, both broad and deep, offers promise that, in the future, liver transplantation will not only be broadly available to those in need but also represent a highly durable life-saving therapy. 

The future of Liver Transplantation

Segmenting the liver and liver tumors in computed tomography (CT) images is an important step toward quantifiable biomarkers for a computer-aided decision-making system and precise medical diagnosis. Radiologists and specialized physicians use CT images to diagnose and classify liver organs and tumors. Because these organs have similar characteristics in form, texture, and light intensity values, other internal organs such as the heart, spleen, stomach, and kidneys confuse visual recognition of the liver and tumor division. Furthermore, visual identification of liver tumors is time-consuming, complicated, and error-prone, and incorrect diagnosis and segmentation can hurt the patient's life. Many automatic and semi-automatic methods based on machine learning algorithms have recently been suggested for liver organ recognition and tumor segmentation. However, there are still difficulties due to poor recognition precision and speed and a lack of dependability. This paper presents a novel deep learning-based technique for segmenting liver tumors and identifying liver organs in computed tomography maps. Based on the LiTS17 database, the suggested technique comprises four Chebyshev graph convolution layers and a fully connected layer that can accurately segment the liver and liver tumors. Thus, the accuracy, Dice coefficient, mean IoU, sensitivity, precision, and recall obtained based on the proposed method according to the LiTS17 dataset are around 99.1%, 91.1%, 90.8%, 99.4%, 99.4%, and 91.2%, respectively. In addition, the effectiveness of the proposed method was evaluated in a noisy environment, and the proposed network could withstand a wide range of environmental signal-to-noise ratios (SNRs). Thus, at SNR = -4 dB, the accuracy of the proposed method for liver organ segmentation remained around 90%. The proposed model has obtained satisfactory and favorable results compared to previous research. According to the positive results, the proposed model is expected to be used to assist radiologists and specialist doctors in the near future.

Automatic Liver Tumor Segmentation from CT Images Using Graph Convolutional Network.

Research on liver transplantation (LT) for liver cancer has gained increasing attention. This paper has comprehensively described the current status, hotspots and trends in this field. A total of 2991 relevant articles from 1 January 1963 to 28 February 2023 were obtained from the Web of Science Core Collection. VOSviewer and CiteSpace software were utilized as bibliometric tools to analyze and visualize knowledge mapping. Between 1963 and 2023, the number of papers in the area of LT for liver cancer increased continuously. A total of 70 countries/regions, 2303 institutions and 14 840 researchers have published research articles, with the United States and China being the two most productive countries. Our bibliometric-based visual analysis revealed the expansion of LT indications for liver cancer and the prevention/treatment of cancer recurrence as ongoing research hotspots over the past decades. Meanwhile, emerging studies also focus on downstaging/bridging treatments before LT and the long-term survival of LT recipient, in particular the precise application of immunosuppressants.

Insights into the history and tendency of liver transplantation for liver cancer: A bibliometric-based visual analysis.

Liver allograft steatosis is a significant risk factor for postoperative graft dysfunction and has been associated with inferior patient and graft survival, particularly in the case of moderate or severe macrovesicular steatosis. In recent years, the increasing incidence of obesity and fatty liver disease in the population has led to a higher proportion of steatotic liver grafts being used for transplantation, making the optimization of their preservation an urgent necessity. This review discusses the mechanisms behind the increased susceptibility of fatty livers to ischemia-reperfusion injury and provides an overview of the available strategies to improve their utilization for transplantation, with a focus on preclinical and clinical evidence supporting donor interventions, novel preservation solutions, and machine perfusion techniques.

/pdf/how-to-preserve-steatotic-liver-grafts-for-transplantation-1gcpd078.pdf

How to Preserve Steatotic Liver Grafts for Transplantation

A randomized-controlled trial of ischemia-free liver transplantation for end-stage liver disease.

The clinical characteristics of patients with acute leukemia or stem cell transplantation exhibiting immune based platelet refractoriness

Dendritic cells (DCs) play a major role in regulating immune responses, but the aberrant phenotype and function of defective DCs in adult acute lymphoblastic leukemia (ALL) remain unclear. Here, B lineage ALL (B-ALL) patients were divided into groups according to different standards. By course of disease: newly diagnosed (ND), complete remission (CR), consolidation (CONS). By stratification: high risk (HR), standard risk (SR). By minimal residual disease (MRD): MRD positive(MRD+), MRD negative (MRD-). The proportion of plasmacytoid DC(pDC) and myeloid DC(mDC) were compared within these standards. The costimulatory molecule levels of pDC, mDC in ND and CR were measured and the function of peripheral blood monocyte-derived DC(MoDC)s were examined. We found proportions of pDC and mDC in ND were both lower compared to control group and gradually increased after CR. In HR and MRD+, the proportions were also lower compared to SR and MRD- at CR stage, respectively; but there were no difference between these comparisons when newly diagnosed. In ND, both CD80, CD86 levels in pDC, mDC were higher while the levels in activated MoDCs were lower when compared to control and CR group, respectively. The dextran uptake of MoDCs, T cell proliferation promoting ability, IL-12, BAFF, INF-α levels in supernatant and their mRNA relative expression in activated MoDCs in ND were also lower than those in control and CR group. So, DCs in B-ALL display suppressed status in phenotype and function，which would be gradually restored after effective chemotherapy. pDC and mDC could respond to patient condition, DCs proportion may be useful for monitoring disease progression.

Aberrant Phenotype and Function of Dendritic Cells in Adult B Lineage Acute Lymphoblastic Leukemia.

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A randomized-controlled trial of ischemia-free liver transplantation for end-stage liver disease.

The clinical characteristics of patients with acute leukemia or stem cell transplantation exhibiting immune based platelet refractoriness

Aberrant Phenotype and Function of Dendritic Cells in Adult B Lineage Acute Lymphoblastic Leukemia.