Autophagy in herpesvirus immune control and immune escape

Autophagy delivers cytoplasmic constituents for lysosomal degradation, and thereby facilitates pathogen degradation and pathogen fragment loading onto MHC molecules for antigen presentation to T cells. Herpesviruses have been used to demonstrate these novel functions of autophagy, which previously has been primarily appreciated for its pro-survival role during starvation. In this review, we summarize recent findings how macroautophagy restricts herpesvirus infections directly, how macroautophagy and chaperone mediated autophagy contribute to herpesviral antigen presentation on MHC molecules, and which mechanisms herpesviruses have developed to interfere with these pathways. These studies suggest that herpesviruses significantly modulate autophagy to escape from its functions in innate and adaptive immunity

Selective binding of the scavenger receptor C-type lectin to Lewisx trisaccharide and related glycan ligands

The scavenger receptor C-type lectin (SRCL) is an endothelial receptor that is similar in organization to type A scavenger receptors for modified low density lipoproteins but contains a C-type carbohydrate-recognition domain (CRD). Fragments of the receptor consisting of the entire extracellular domain and the CRD have been expressed and characterized. The extracellular domain is a trimer held together by collagen-like and coiled-coil domains adjacent to the CRD. The amino acid sequence of the CRD is very similar to the CRD of the asialoglycoprotein receptor and other galactose-specific receptors, but SRCL binds selectively to asialo-orosomucoid rather than generally to asialoglycoproteins. Screening of a glycan array and further quantitative binding studies indicate that this selectivity results from high affinity binding to glycans bearing the Lewis(x) trisaccharide. Thus, SRCL shares with the dendritic cell receptor DC-SIGN the ability to bind the Lewis(x) epitope. However, it does so in a fundamentally different way, making a primary binding interaction with the galactose moiety of the glycan rather than the fucose residue. SRCL shares with the asialoglycoprotein receptor the ability to mediate endocytosis and degradation of glycoprotein ligands. These studies suggest that SRCL might be involved in selective clearance of specific desialylated glycoproteins from circulation and/or interaction of cells bearing Lewis(x)-type structures with the vascular endothelium

Rapidly Evolving Giant Dermatofibroma

Dermatofibroma, also known as “fibrous histiocytoma”, is a benign dermal or subcutaneous poorly circumscribed proliferation of spindle-shaped fibroblasts and macrophages in the dermis. Although it is commonly present as a brownish nodule the legs of females, it may also arise on the upper extremities, trunk, and rarely on the head. The exact pathogenesis is unclear. However, it is widely believed that the originating insult to the dermis is a folliculitis, an arthropod bite, or an unspecified initial inflammatory condition. Giant dermatofibromas of greater than 5 cm in diameter are rare, with only 22 cases reported in the literature. We present a case of a rapidly evolving pedunculated mass in the groin of a male patient. Histological examination confirmed this to be a giant dermatofibroma. Though this specimen cannot is not confirmed as such, the cellular subtype is sometimes present as a larger lesion with anecdotal reports of local recurrence and distant metastases. The clinical and radiological features which were somewhat suspicious of malignancy are considered in the context of the definitive pathological diagnosis of a benign lesion

Role of AI and digital pathology for colorectal immuno-oncology

Immunotherapy deals with therapeutic interventions to arrest the progression of tumours using the immune system. These include checkpoint inhibitors, T-cell manipulation, cytokines, oncolytic viruses and tumour vaccines. In this paper, we present a survey of the latest developments on immunotherapy in colorectal cancer (CRC) and the role of artificial intelligence (AI) in this context. Among these, microsatellite instability (MSI) is perhaps the most popular IO biomarker globally. We first discuss the MSI status of tumours, its implications for patient management, and its relationship to immune response. In recent years, several aspiring studies have used AI to predict the MSI status of patients from digital whole-slide images (WSIs) of routine diagnostic slides. We present a survey of AI literature on the prediction of MSI and tumour mutation burden from digitised WSIs of haematoxylin and eosin-stained diagnostic slides. We discuss AI approaches in detail and elaborate their contributions, limitations and key takeaways to drive future research. We further expand this survey to other IO-related biomarkers like immune cell infiltrates and alternate data modalities like immunohistochemistry and gene expression. Finally, we underline possible future directions in immunotherapy for CRC and promise of AI to accelerate this exploration for patient benefits

A response to “Likelihood ratio as weight of evidence: a closer look” by Lund and Iyer

Recently, Lund and Iyer (L&I) raised an argument regarding the use of likelihood ratios in court. In our view, their argument is based on a lack of understanding of the paradigm. L&I argue that the decision maker should not accept the expert’s likelihood ratio without further consideration. This is agreed by all parties. In normal practice, there is often considerable and proper exploration in court of the basis for any probabilistic statement. We conclude that L&I argue against a practice that does not exist and which no one advocates. Further we conclude that the most informative summary of evidential weight is the likelihood ratio. We state that this is the summary that should be presented to a court in every scientific assessment of evidential weight with supporting information about how it was constructed and on what it was based