MHC Hammer reveals genetic and non-genetic HLA disruption in cancer evolution.

Disruption of the class I human leukocyte antigen (HLA) molecules has important implications for immune evasion and tumor evolution. We developed major histocompatibility complex loss of heterozygosity (LOH), allele-specific mutation and measurement of expression and repression (MHC Hammer). We identified extensive variability in HLA allelic expression and pervasive HLA alternative splicing in normal lung and breast tissue.

Fcγ receptors and immunomodulatory antibodies in cancer.

The discovery of both cytotoxic T lymphocyte-associated antigen 4 (CTLA4) and programmed cell death protein 1 (PD1) as negative regulators of antitumour immunity led to the development of numerous immunomodulatory antibodies as cancer treatments. Preclinical studies have demonstrated that the efficacy of immunoglobulin G (IgG)-based therapies depends not only on their ability to block or engage their targets but also on the antibody's constant region (Fc) and its interactions with Fcγ receptors (FcγRs). Fc-FcγR interactions are essential for the activity of tumour-targeting antibodies, such as rituximab, trastuzumab and cetuximab, where the killing of tumour cells occurs at least in part due to these mechanisms.

Inhibition of lactate transport by MCT-1 blockade improves chimeric antigen receptor T-cell therapy against B-cell malignancies.

Background: Chimeric antigen receptor (CAR) T cells have shown remarkable results against B-cell malignancies, but only a minority of patients have long-term remission. The metabolic requirements of both tumor cells and activated T cells result in production of lactate. The export of lactate is facilitated by expression of monocarboxylate transporter (MCTs).

Glioblastoma cell fate is differentially regulated by the microenvironments of the tumor bulk and infiltrative margin.

Glioblastoma (GBM) recurrence originates from invasive margin cells that escape surgical debulking, but to what extent these cells resemble their bulk counterparts remains unclear. Here, we generated three immunocompetent somatic GBM mouse models, driven by subtype-associated mutations, to compare matched bulk and margin cells. We find that, regardless of mutations, tumors converge on common sets of neural-like cellular states.

The tumour ecology of quiescence: Niches across scales of complexity.

Quiescence is a state of cell cycle arrest, allowing cancer cells to evade anti-proliferative cancer therapies. Quiescent cancer stem cells are thought to be responsible for treatment resistance in glioblastoma, an aggressive brain cancer with poor patient outcomes. However, the regulation of quiescence in glioblastoma cells involves a myriad of intrinsic and extrinsic mechanisms that are not fully understood.

Dopaminergic Signalling Enhances IL-2 Production and Strengthens Anti-Tumour Response Exerted by Cytotoxic T Lymphocytes in a Melanoma Mouse Model.

Dopamine has emerged as an important regulator of immunity. Recent evidence has shown that signalling through low-affinity dopamine receptors exerts anti-inflammatory effects, whilst stimulation of high-affinity dopamine receptors potentiates immunity in different models. However, the dopaminergic regulation of CD8 T-cells in anti-tumour immunity remains poorly explored.

Glioblastomas acquire myeloid-affiliated transcriptional programs via epigenetic immunoediting to elicit immune evasion.

Glioblastoma multiforme (GBM) is an aggressive brain tumor for which current immunotherapy approaches have been unsuccessful. Here, we explore the mechanisms underlying immune evasion in GBM. By serially transplanting GBM stem cells (GSCs) into immunocompetent hosts, we uncover an acquired capability of GSCs to escape immune clearance by establishing an enhanced immunosuppressive tumor microenvironment.

Tissue-resident memory CD8 T cells amplify anti-tumor immunity by triggering antigen spreading through dendritic cells.

Tissue-resident memory CD8 T (Trm) cells mediate potent local innate and adaptive immune responses and play a central role against solid tumors. However, whether Trm cells cross-talk with dendritic cells (DCs) to support anti-tumor immunity remains unclear. Here we show that antigen-specific activation of skin Trm cells leads to maturation and migration to draining lymph nodes of cross-presenting dermal DCs.

Analysis of Tissue-Resident Immune Cells from Mouse Skin and Lungs by Flow Cytometry.

The heterogeneity and complexity of nonlymphoid tissues has become a major obstacle for the study of immune populations. For this reason, the generation of highly reproducible protocols that allow the analysis of immune cells in these tissues has become crucial for clinical and preclinical research. Here we describe an optimized method that allows the obtention of single-cell suspensions from the skin and lungs to analyze and quantify populations of tissue-resident memory CD8 T cells by multi-parametric flow cytometry.

Vaccination-induced skin-resident memory CD8 T cells mediate strong protection against cutaneous melanoma.

Memory CD8 T cell responses have the potential to mediate long-lasting protection against cancers. Resident memory CD8 T (Trm) cells stably reside in non-lymphoid tissues and mediate superior innate and adaptive immunity against pathogens. Emerging evidence indicates that Trm cells develop in human solid cancers and play a key role in controlling tumor growth.

The function and dysfunction of memory CD8 T cells in tumor immunity.

The generation and maintenance of CD8 T cell memory is crucial to long-term host survival, yet the basic tenets of CD8 T cell immunity are still being established. Recent work has led to the discovery of tissue-resident memory cells and refined our understanding of the transcriptional and epigenetic basis of CD8 T cell differentiation and dysregulation. In parallel, the unprecedented clinical success of immunotherapy has galvanized an intense, global research effort to decipher and de-repress the anti-tumor response.

-Generated Tc17 Cells Present a Memory Phenotype and Serve As a Reservoir of Tc1 Cells .

Memory CD8 T cells are ideal candidates for cancer immunotherapy because they can mediate long-term protection against tumors. However, the therapeutic potential of different -generated CD8 T cell effector subsets to persist and become memory cells has not been fully characterized. Type 1 CD8 T (Tc1) cells produce interferon-γ and are endowed with high cytotoxic capacity, whereas IL-17-producing CD8 T (Tc17) cells are less cytotoxic but display enhanced self-renewal capacity.

Paracetamol (acetaminofeno) intravenoso para cierre de conducto arterioso permeable en prematuros ≤ 32 semanas de gestación.

Objective: To identify the effectiveness of intravenous paracetamol for closure of patent ductus arteriosus in preterm ≤32 weeks gestation.

Method: This was a series of cases, a therapeutic intervention to closure was applied for ductus arteriosus >2 mm, identified by echocardiogram after 3 days of life, intravenous paracetamol was used, for a time range from 3 up to 6 days.

Results: The prevalence of patent ductus arteriosus in ≤32 weeks gestation, was 40%.

Caveolin-1 Expression Increases upon Maturation in Dendritic Cells and Promotes Their Migration to Lymph Nodes Thereby Favoring the Induction of CD8 T Cell Responses.

Dendritic cell (DC) trafficking from peripheral tissues to lymph nodes (LNs) is a key step required to initiate T cell responses against pathogens as well as tumors. In this context, cellular membrane protrusions and the actin cytoskeleton are essential to guide DC migration towards chemotactic signals. Caveolin-1 (CAV1) is a scaffolding protein that modulates signaling pathways leading to remodeling of the actin cytoskeleton and enhanced migration of cancer cells.

A short hairpin RNA-based adjuvant targeting NF-κB repressor IκBα promotes migration of dermal dendritic cells to draining lymph nodes and antitumor CTL responses induced by DNA vaccination.

DNA vaccination is an attractive approach to elicit tumor-specific cytotoxic CD8 T lymphocytes (CTL), which can mediate protective immunity against tumors. To initiate CTL responses, antigen-encoding plasmids employed for DNA vaccination need to activate dendritic cells (DC) through the stimulation of DNA-sensing innate immune receptors that converge in the activation of the master transcription factor NF-κB. To this end, NF-κB repressor IκBα needs to be degraded, allowing NF-κB to translocate to the nucleus and transcribe proinflammatory target genes, as well as its repressor IκBα.

Inhibition of dopamine receptor D3 signaling in dendritic cells increases antigen cross-presentation to CD8 T-cells favoring anti-tumor immunity.

Dendritic cells (DCs) display the unique ability for cross-presenting antigens to CD8 T-cells, promoting their differentiation into cytotoxic T-lymphocytes (CTLs), which play a pivotal role in anti-tumor immunity. Emerging evidence points to dopamine receptor D3 (D3R) as a key regulator of immunity. Accordingly, we studied how D3R regulates DCs function in anti-tumor immunity.

Cripto-1 vaccination elicits protective immunity against metastatic melanoma.

Metastatic melanoma is a fatal disease that responds poorly to classical treatments but can be targeted by T cell-based immunotherapy. Cancer vaccines have the potential to generate long-lasting cytotoxic CD8(+) T cell responses able to eradicate established and disseminated tumors. Vaccination against antigens expressed by tumor cells with enhanced metastatic potential represents a highly attractive strategy to efficiently target deadly metastatic disease.

[Cardiac tamponade associated with umbilical venous catheter (UVC) placed in inappropriate position].

Umbilical venous catheter (UVC) is widely used in neonatal intensive care units. Pericardial effusion is an uncommon but life-threatening complication; and tamponade have been reported in 3% of neonates having such catheters. We present a case of cardiac tamponade as a complication of venous catheter in a neonate.

[Percutaneous closure of the patent ductus arteriosus in children with the Amplatzer Duct Occluder II].

Introduction: In the last decades, several devices have been used for the percutaneous closure of patent ductus arteriosus, with its own limitations and risks. The Amplatzer Duct Occluder II has been designed to overcome those limitations and reduce risks.

Objective: We described our initial series of patients who underwent percutaneous closure of patent ductus arteriosus with the Amplatzer Duct Occluder II, emphasis on the technical aspects of the procedure.