Antigen presenting capacity of murine splenic myeloid cells

BACKGROUND: The spleen is an important site for hematopoiesis. It supports development of myeloid cells from bone marrow-derived precursors entering from blood. Myeloid subsets in spleen are not well characterised although dendritic cell (DC) subsets are clearly defined in terms of phenotype, development and functional role. Recently a novel dendritic-like cell type in spleen named ‘L-DC’ was distinguished from other known dendritic and myeloid cells by its distinct phenotype and developmental origin. That study also redefined splenic eosinophils as well as resident and inflammatory monocytes in spleen. RESULTS: L-DC are shown to be distinct from known splenic macrophages and monocyte subsets. Using a new flow cytometric procedure, it has been possible to identify and isolate L-DC in order to assess their functional competence and ability to activate T cells both in vivo and in vitro. L-DC are readily accessible to antigen given intravenously through receptor-mediated endocytosis. They are also capable of CD8(+) T cell activation through antigen cross presentation, with subsequent induction of cytotoxic effector T cells. L-DC are MHCII(−) cells and unable to activate CD4(+) T cells, a property which clearly distinguishes them from conventional DC. The myeloid subsets of resident monocytes, inflammatory monocytes, neutrophils and eosinophils, were found to have varying capacities to take up antigen, but were uniformly unable to activate either CD4(+) T cells or CD8(+) T cells. CONCLUSION: The results presented here demonstrate that L-DC in spleen are distinct from other myeloid cells in that they can process antigen for CD8(+) T cell activation and induction of cytotoxic effector function, while both L-DC and myeloid subsets remain unable to activate CD4(+) T cells. The L-DC subset in spleen is therefore distinct as an antigen presenting cell

Characterisation of a novel dendritic-like cell in spleen

Dendritic cells (DC) are specialised antigen presenting cells, which induce and control the adaptive immune response. DC mediate a wide range of immune responses including generation of T helper cells, development of cytotoxic T cell responses and induction of tolerance. In this lab, a splenic longterm culture (LTC) was established that produces distinct dendritic-like cells (LTC-DC) continuously in the absence of added growth factors or cytokines. Previous studies have identified an in vivo equivalent of LTC-DC in murine spleen. This thesis further characterises this novel dendritic-like subset (L-DC). The relationship between L-DC and other known dendritic and myeloid subsets has also been investigated through phenotypic, morphological and functional studies, by comparing gene expression, and by analysis of cell development in mutant mouse models. In order to identify L-DC, it was necessary to redefine splenic dendritic and myeloid subsets. L-DC have now been characterised with the CD11bhiCD11cloMHCII-Ly6C-Ly6G-CD43+CX3CR1+Siglec-F- phenotype. CD43 expression, lack of MHCII expression, and a low level of CD11c expression best differentiate L-DC from conventional DC (cDC). Like CD8+ cDC, L-DC have high capacity for receptor-medicated endocytosis and induce activation and proliferation of CD8+ T cells, although not CD4+ T cells. L-DC also show capacity to induce an in vivo cytotoxic T lymphocyte response equivalent to that induced by CD8+ cDC. L-DC are distinguishable from neutrophils by the absence of Ly6G and 7/4 expression, and from eosinophils by lack of Siglec-F expression. L-DC can be distinguished from monocytes by their lack Ly6C expression. Morphological studies revealed L-DC to be mononuclear cells with vacuoles in the cytoplasm, and distinct from other myeloid cell types. All of these findings have identified L-DC as a novel antigen presenting cell subset, distinct from other known dendritic and myeloid subsets in murine spleen. Attempts have been made to understand the lineage relationship between L-DC and the other splenic dendritic and myeloid subsets, and to identify new markers for easier delineation of L-DC. Transcriptome analysis (Affymetrix) was performed on L-DC, dendritic and myeloid subsets. The L-DC gene expression profile was found to be distinct from that of cDC. However, the L-DC gene expression profile was also found to be distinct from that of monocytes subsets. L-DC specifically expressed genes like Siglec-e, Igsf2, CD300ld, CD300e and CD9. Overall, gene expression analysis showed that L-DC resembled a myeloid lineage cell having dendritic-like characteristics and function in antigen presentation. Mouse strains carrying mutations which affect the development of dendritic and myeloid cell types were investigated for changes in L-DC development in spleen. However L-DC numbers were not altered in any of the mutant mice studied, suggesting that L-DC is a distinct lineage of cells that arise from endogenous splenic progenitors, separate from the dendritic and monocyte. This study has revealed a novel dendritic-like cell type distinct from known dendritic and myeloid subsets in spleen, and having specialised function in cross-priming CD8+ T cells. The findings presented here predict an important role for L-DC in the immune response against blood-borne antigens which enter the splenic microenvironment

The molecular characteristics of recurrent/metastatic HPV-positive head and neck squamous cell carcinoma:A systematic review of the literature

Objectives: About 17% of patients with human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC), which is mainly comprised of oropharyngeal SCC (OPSCC), will experience disease recurrence, which is often considered incurable when manifested at a metastatic and/or recurrent stage. We conducted a critical qualitative systematic review. Our objectives were to provide an overview of the molecular landscape of recurrent/metastatic HPV-positive HNSCC as well as novel molecular biomarkers. Design: A literature review was conducted to identify studies reporting on the molecular characteristics of recurrent/metastatic HPV-positive HNSCC, novel molecular biomarkers and treatment options. The reviews of abstracts, full articles, and revision of the included studies, followed by data extraction and quality assessment were performed by three independent assessors. All primary literature, such as retrospective, prospective, and clinical trials as well as basic research studies were considered, and the final search was conducted at the end of February 2023. The level of evidence was rated using the guidelines published by the Oxford Centre for Evidence-based Medicine and quality was assessed using the Newcastle-Ottawa Scale criteria. Results and Conclusions: The literature search resulted in the identification of 1991 articles. A total of 181 full articles were screened, and 66 articles were included in this analysis. Several studies reported that recurrent/metastatic HPV-positive HNSCC had higher rates of TP53 mutation and were genomically similar to HPV-negative HNSCC. The detection of circulating tumour tissue-modified HPV DNA (ctHPVDNA) as a specific biomarker has shown promising results for monitoring treatment response and recurrence in the subset of HPV-positive HNSCC. In addition, evidence for targeted therapy in recurrent/metastatic HPV-positive HNSCC has emerged, including agents that inhibit overexpressed EGFR. Studies of combination immunotherapy are also underway. Our review outlines the latest evidence on the distinct molecular profiles of recurrent/metastatic HPV-positive HNSCC as well as the clinical potential of ctHPVDNA testing in routine practice. More controlled and longitudinal studies are needed to identify additional molecular targets and to assess the performance and benefits of novel molecular biomarkers in clinical practice.</p

Spleen as a Site for Hematopoiesis of a Distinct Antigen Presenting Cell Type

While spleen and other secondary tissue sites contribute to hematopoiesis, the nature of cells produced and the environment under which this happens are not fully defined. Evidence is reviewed here for hematopoiesis occurring in the spleen microenvironment leading to the production of tissue-specific antigen presenting cells. The novel dendritic-like cell identified in spleen is phenotypically and functionally distinct from other described antigen presenting cells. In order to identify these cells as distinct, it has been necessary to show that their lineage origin and progenitors differ from that of other known dendritic and myeloid cell types. The spleen therefore represents a distinct microenvironment for hematopoiesis of a novel myeloid cell arising from self-renewing hematopoietic stem cells (HSC) or progenitors endogenous to spleen

Outpatient (Same‐day Discharge) versus Inpatient Parotidectomy:A Systematic Review and Meta‐analysis

Background: Parotidectomy is often performed as an inpatient procedure largely due to drain insertion; however, outpatient parotidectomy has increasingly become an attractive alternative for its shorter hospital stays and greater efficiency in cost-effectiveness. Objective of review: To assess the safety and feasibility of outpatient (or same-day discharge) parotidectomy compared with inpatient parotidectomy. Type of review: Systematic review of the literature and meta-analysis, in accordance with the PRISMA guidelines.Methods: Pubmed/Medline, Embase, CINAHL, Google Scholar, Web of Science, The Cochrane Library, Cochrane Central Register of Controlled Trials (CENTRAL) were searched for articles published in English between 01/01/1990 and 05/10/2019. The Newcastle-Ottawa Scale was used for quality assessment and Review Manager 5.3 for meta-analyses.Main outcome measures: Primary outcomes assessed were postoperative complications including bleeding/haematoma, surgical site infection, seroma and facial weakness. Secondary outcome was readmission rate.Results: Out of 445 studies identified, 6 were selected for systematic review. The overall quality of evidence was moderate. A total of 3664 patients were included (1646 in the outpatient group and 2018 in the inpatient group). Comparing the outpatient with inpatient cohorts, there were lower complications in outpatient groups though not statistically significant for haematoma (OR = 0.45; 95% CI = 0.11-1.92; P =.28), surgical site infection (OR = 0.88; 95% CI = 0.46-1.69; P =.70), seroma (0.79; 95% CI = 0.21-3.03; P =.74), facial nerve weakness (OR 0.39; 95% CI = 0.14-1.08; P =.07) and hospital readmission (OR 0.58; 95% CI = 0.33-1.04; P =.07).Conclusions: Outpatient parotidectomy appears to be safe and compares favourably to inpatient procedure in postoperative complication and readmission rates.</p

A mixed methods comparative evaluation of a low cost otoscope (Arclight) with a traditional device in twenty-one clinicians

According to the World Health Organisation estimate, the global burden of illness from chronic ear infection affects about 4% of the world population (up to 330 million) with ear discharge and 60% of whom (up to 200 million) suffer from significant hearing impairment.1 Alarmingly, over 90% of the burden of chronic ear infections is borne by low‐ and middle‐income countries (LMICs).PostprintPeer reviewe