Cancer associated fibroblasts: the architects of stroma remodelling

Fibroblasts have exceptional phenotypic plasticity and capability to secrete vast amount of soluble factors, ECM components and extracellular vesicles. While in physiological conditions this makes fibroblasts master regulators of tissue homeostasis and healing of injured tissues, in solid tumours cancer-associated fibroblasts (CAFs) co-evolve with the disease, and alter the biochemical and physical structure of the tumour microenvironment, as well as the behaviour of the surrounding stromal and cancer cells. Thus CAFs are fundamental regulators of tumour progression and influence response to therapeutic treatments. Increasing efforts are devoted to better understand the biology of CAFs to bring insights to develop complementary strategies to target this cell type in cancer. Here we highlight components of the tumour microenvironment that play key roles in cancer progression and invasion, and provide an extensive overview of past and emerging understanding of CAF biology as well as the contribution that mass spectrometry (MS)-based proteomics has made to this field

Newborn Screening for Severe Combined Immunodeficiency in Israel

Newborn screening (NBS) programs for severe combined immunodeficiency (SCID), the most severe type of primary immunodeficiency, are being implemented in more and more countries with every passing year. Since October 2015, SCID screening via T cell receptor excision circle (TREC) quantification in dried blood spots (DBS) has been part of the Israeli NBS program. As an NBS program in its infancy, SCID screening is still evolving, making gathering input from the various programs crucial for compiling an ideal screening algorithm. The relatively high rate of consanguineous marriages in Israel, especially among non-Jews, correlates with an increased incidence of SCID. The Israeli algorithm uses a commercial kit and consists of a two-Guthrie card confirmation system prior to referral to a national immunology center. Preliminary data from the first year and a half of SCID screening in Israel has identified a surprisingly high prevalence of DNA cross-link repair protein 1c (DCLRE1C; ARTEMIS) mutations as the cause of SCID in Israel. The clinically unbiased nature of SCID screening helps unearth mild/leaky SCID phenotypes, resulting in a better understanding of true SCID prevalence and etiology

Increased RNA Editing May Provide a Source for Autoantigens in Systemic Lupus Erythematosus

Summary: RNA-editing mechanisms, which induce nucleotide substitution in the RNA, increase transcript and protein diversities. Editing dysregulation has been shown to lead to grave outcomes, and transcriptome-wide aberrant RNA editing has been found in tumors. However, little is known about the involvement of editing in other diseases. Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease characterized by a loss of tolerance for autoantigens from various tissues and the production of multiple autoantibodies. Here, we show that blood samples from individuals with SLE have abnormally high levels of RNA editing, some of which affect proteins and potentially generate novel autoantigens. We suggest that elevated RNA editing, either by ADARs or APOBECs, may be involved in the pathophysiology of SLE, as well as in other autoimmune diseases, by generating or increasing the autoantigen load, a key requisite for the progression of autoimmunity. : Roth et al. show that SLE patients have elevated RNA editing, a process that modifies an RNA sequence from the sequence encoded in the genome. This is manifested as both increased numbers and various altered coding sequences, which may promote autoimmune progression by increasing autoantigenic load. Keywords: systemic lupus erythematosus, SLE, RNA editing, autoimmune disease, immune tolerance, ADAR, APOBEC3, neo-autoantigens, A-to-I editing, C-to-U editin