Dendritic cells type 1 control the formation, maintenance, and function of tertiary lymphoid structures in cancer.

Tertiary lymphoid structures (TLS) are organized immune cell aggregates that arise in chronic inflammatory conditions. In cancer, TLS are associated with better prognosis and enhanced response to immunotherapy, making these structures attractive therapeutic targets. However, the mechanisms regulating TLS formation and maintenance in cancer are incompletely understood.

MacroH2A restricts inflammatory gene expression in melanoma cancer-associated fibroblasts by coordinating chromatin looping.

MacroH2A has established tumour suppressive functions in melanoma and other cancers, but an unappreciated role in the tumour microenvironment. Using an autochthonous, immunocompetent mouse model of melanoma, we demonstrate that mice devoid of macroH2A variants exhibit increased tumour burden compared with wild-type counterparts. MacroH2A-deficient tumours accumulate immunosuppressive monocytes and are depleted of functional cytotoxic T cells, characteristics consistent with a compromised anti-tumour response.

Selective STING stimulation in dendritic cells primes antitumor T cell responses.

T cells that recognize tumor antigens are crucial for mounting antitumor immune responses. Induction of antitumor T cells in immunogenic tumors depends on STING, the intracellular innate immune receptor for cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) and related cyclic dinucleotides (CDNs). However, the optimal way to leverage STING activation in nonimmunogenic tumors is still unclear.

Spatial Positioning and Matrix Programs of Cancer-Associated Fibroblasts Promote T-cell Exclusion in Human Lung Tumors.

Unlabelled: It is currently accepted that cancer-associated fibroblasts (CAF) participate in T-cell exclusion from tumor nests. To unbiasedly test this, we used single-cell RNA sequencing coupled with multiplex imaging on a large cohort of lung tumors. We identified four main CAF populations, two of which are associated with T-cell exclusion: (i) MYH11+αSMA+ CAF, which are present in early-stage tumors and form a single cell layer lining cancer aggregates, and (ii) FAP+αSMA+ CAF, which appear in more advanced tumors and organize in patches within the stroma or in multiple layers around tumor nests.

Single-cell analysis of human non-small cell lung cancer lesions refines tumor classification and patient stratification.

Immunotherapy is a mainstay of non-small cell lung cancer (NSCLC) management. While tumor mutational burden (TMB) correlates with response to immunotherapy, little is known about the relationship between the baseline immune response and tumor genotype. Using single-cell RNA sequencing, we profiled 361,929 cells from 35 early-stage NSCLC lesions.

Viscous Core Liposomes Increase siRNA Encapsulation and Provides Gene Inhibition When Slightly Positively Charged.

Since its discovery, evidence that siRNA was able to act as an RNA interference effector, led to its acceptation as a novel medicine. The siRNA approach is very effective, due to its catalytic mechanism, but still the limitations of its cellular delivery should be addressed. One promising form of non-viral gene delivery system is liposomes.

Single-Cell Analysis of Crohn's Disease Lesions Identifies a Pathogenic Cellular Module Associated with Resistance to Anti-TNF Therapy.

Clinical benefits of cytokine blockade in ileal Crohn's disease (iCD) are limited to a subset of patients. Here, we applied single-cell technologies to iCD lesions to address whether cellular heterogeneity contributes to treatment resistance. We found that a subset of patients expressed a unique cellular module in inflamed tissues that consisted of IgG plasma cells, inflammatory mononuclear phagocytes, activated T cells, and stromal cells, which we named the GIMATS module.

Host tissue determinants of tumour immunity.

Although common evolutionary principles drive the growth of cancer cells regardless of the tissue of origin, the microenvironment in which tumours arise substantially differs across various organ sites. Recent studies have established that, in addition to cell-intrinsic effects, tumour growth regulation also depends on local cues driven by tissue environmental factors. In this Review, we discuss how tissue-specific determinants might influence tumour development and argue that unravelling the tissue-specific contribution to tumour immunity should help the development of precise immunotherapeutic strategies for patients with cancer.

Europium labeled lactosylated albumin as a model workflow for the development of biotherapeutics.

Lactosylated albumin is currently used as a radiopharmaceutical agent to image the liver asialoglycoprotein receptors and quantify hepatic liver function in various diseases. A lactosylated protein (LACTAL) conjugate showed excellent liver uptake compared to non-lactosylated protein and a high signal to noise ratio, based on the biodistribution in mice using Tc-scintigraphy. However, in the laboratory, it is useful to have a method that can be used in daily practice to quantify cellular targeting or biodistribution.

Immunomodulating effect of a seaweed extract from in pig: Specific IgG and total IgA in colostrum, milk, and blood.

The transfer of passive immunity from sows to piglets can be improved through the administration of immuno-stimulating products before farrowing. This study evaluated the immuno-stimulating effect of an algal sulfated polysaccharide extract (MSP extract) from the green algae when administrated orally to sows at the end of gestation. Four diets were tested: Control (no MSP extract), MSP1 (2 g/day of MSP extract), MSP2 (8 g/day), and MSP3 (16 g/day).

Assessment of the targeting specificity of a fluorescent albumin conceived as a preclinical agent of the liver function.

In the context of increasing liver diseases, no contrast agent is currently available in Europe and the United States to directly assess the liver function. Only neolactosylated human serum albumin is being clinically used in Asia. In order to perform preclinical studies in the context of liver diseases, we conceived a fluorescent lactosylated albumin for the quantification of liver functional cells (l-Cyal).

EMT- and stroma-related gene expression and resistance to PD-1 blockade in urothelial cancer.

Cancers infiltrated with T-cells are associated with a higher likelihood of response to PD-1/PD-L1 blockade. Counterintuitively, a correlation between epithelial-mesenchymal transition (EMT)-related gene expression and T-cell infiltration has been observed across tumor types. Here we demonstrate, using The Cancer Genome Atlas (TCGA) urothelial cancer dataset, that although a gene expression-based measure of infiltrating T-cell abundance and EMT-related gene expression are positively correlated, these signatures convey disparate prognostic information.

Radiation therapy facility risk analysis in Brazil with SEVRRA software.

Risk assessment deals with processes, accident-initiating events, barriers and risk ratings to unveil the fragility and weakness of some processes; within this study, specifically related to radiation therapy facilities. Barriers are technical or organizational safety measures put in place to avoid, prevent, detect, control, reduce or mitigate the consequences of an accident once an initiating event has occurred. In this work, radiological risk analysis was performed for a set of 20 Brazilian radiotherapy facilities making use of the freeware sevrra risk-management software.

Notch Signaling Facilitates In Vitro Generation of Cross-Presenting Classical Dendritic Cells.

The IRF8-dependent subset of classical dendritic cells (cDCs), termed cDC1, is important for cross-priming cytotoxic T cell responses against pathogens and tumors. Culture of hematopoietic progenitors with DC growth factor FLT3 ligand (FLT3L) yields very few cDC1s (in humans) or only immature "cDC1-like" cells (in the mouse). We report that OP9 stromal cells expressing the Notch ligand Delta-like 1 (OP9-DL1) optimize FLT3L-driven development of cDC1s from murine immortalized progenitors and primary bone marrow cells.

The Impact of Dose Rate on the Accuracy of Step-and-Shoot Intensity-modulated Radiation Therapy Quality Assurance Using Varian 2300CD.

Introduction: Intensity-modulated radiation therapy (IMRT) delivery using "step-and-shoot" technique on Varian C-Series linear accelerator (linac) is influenced by the communication frequency between the multileaf collimator and linac controllers. Hence, the dose delivery accuracy is affected by the dose rate.

Aim: Our aim was to quantify the impact of using two dose rates on plan quality assurance (QA).

RAF/MEK/extracellular signal-related kinase pathway suppresses dendritic cell migration and traps dendritic cells in Langerhans cell histiocytosis lesions.

Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia characterized by granulomatous lesions containing pathological CD207 dendritic cells (DCs) with constitutively activated mitogen-activated protein kinase (MAPK) pathway signaling. Approximately 60% of LCH patients harbor somatic V600E mutations localizing to CD207 DCs within lesions. However, the mechanisms driving V600E LCH cell accumulation in lesions remain unknown.

Effect of therapeutic doses of radiotherapy on the organic and inorganic contents of the deciduous enamel: an in vitro study.

Objectives: This study evaluated the effects of radiotherapy on the composition of deciduous teeth enamel using micro-energy-dispersive X-ray fluorescence and Fourier transform Raman spectroscopy before and after a pH cycling process.

Materials And Methods: Ten deciduous molars were sectioned and divided into two groups (n = 10). The radiotherapy group (RT) was irradiated with 54 Gy at 2 Gy/day, 5 days per week for 5 weeks and 2 days, and the normal group (N) was not irradiated.

Expansion and Activation of CD103(+) Dendritic Cell Progenitors at the Tumor Site Enhances Tumor Responses to Therapeutic PD-L1 and BRAF Inhibition.

Large numbers of melanoma lesions develop resistance to targeted inhibition of mutant BRAF or fail to respond to checkpoint blockade. We explored whether modulation of intratumoral antigen-presenting cells (APCs) could increase responses to these therapies. Using mouse melanoma models, we found that CD103(+) dendritic cells (DCs) were the only APCs transporting intact antigens to the lymph nodes and priming tumor-specific CD8(+) T cells.

CDKN1A regulates Langerhans cell survival and promotes Treg cell generation upon exposure to ionizing irradiation.

Treatment with ionizing radiation (IR) can lead to the accumulation of tumor-infiltrating regulatory T cells (Treg cells) and subsequent resistance of tumors to radiotherapy. Here we focused on the contribution of the epidermal mononuclear phagocytes Langerhans cells (LCs) to this phenomenon because of their ability to resist depletion by high-dose IR. We found that LCs resisted apoptosis and rapidly repaired DNA damage after exposure to IR.

Cost effectiveness of collagen crosslinking for progressive keratoconus in the UK NHS.

Background: Keratoconus is a progressive degenerative corneal disorder of children and young adults that is traditionally managed by refractive error correction, with corneal transplantation reserved for the most severe cases. UVA collagen crosslinking is a novel procedure that aims to prevent disease progression, currently being considered for use in the UK NHS. We assess whether it might be a cost-effective alternative to standard management for patients with progressive keratoconus.

Cancer: A dendritic-cell brake on antitumour immunity.

Activation of a cellular stress response and the transcription factor XBP1 in dendritic cells has now been shown to limit the cells' ability to stimulate antitumour immune responses in a mouse model of ovarian cancer.

Defining Mononuclear Phagocyte Subset Homology Across Several Distant Warm-Blooded Vertebrates Through Comparative Transcriptomics.

Mononuclear phagocytes are organized in a complex system of ontogenetically and functionally distinct subsets, that has been best described in mouse and to some extent in human. Identification of homologous mononuclear phagocyte subsets in other vertebrate species of biomedical, economic, and environmental interest is needed to improve our knowledge in physiologic and physio-pathologic processes, and to design intervention strategies against a variety of diseases, including zoonotic infections. We developed a streamlined approach combining refined cell sorting and integrated comparative transcriptomics analyses which revealed conservation of the mononuclear phagocyte organization across human, mouse, sheep, pigs and, in some respect, chicken.