Autoimmunity and cancer
In autoimmune diseases the immune system attacks and progressively destroys our own, normal tissues. In cancer, the relationship is the reverse; the immune system is unable or prevented in various ways to attack the cancer cells. Novel cancer treatments that activate the immune system are often effective but can cause autoimmune diseases as an adverse reaction - and in chronic, autoimmune diseases there is an increased risk of cancerous transformation of immune cells. These conditions reflect how delicate the balance of the immune system is, and emphasize the importance of building knowledge to understand cellular and molecular immunoregulatory mechanisms in order to develop prevention and new treatments.
Sjögren's syndrome is an autoimmune rheumatic disease that affects secretory glands, predominantly the salivary and lacrimal glands. Muscles and joints can also be affected and many patients experience great fatigue. Some patients also develop extraglandular manifestations involving eg the skin, lungs and kidneys. As part of the autoimmune process, the patients have commonly developed specific autoantibodies. In pregnancy, these autoantibodies pass over the placenta to the fetus and can cause neonatal lupus erythematosus, which includes a congenital heart block. We investigate the pathogenesis of the autoimmune inflammatory process in patients with Sjögren's syndrome and how the fetus is affected during pregnancy in women with Sjögren-associated autoantibodies. The aim is to identify underlying causes, both genetic and environmental factors, and to understand the resulting, disease-causing immunological process. Studies are performed with patients, in experimental models and in vitro. These projects are led by Professor Marie Wahren-Herlenius.
Interferons are a family of cytokines that have a crucial role in the immune system against pathogens, but are also involved in autoimmune diseases and cancer. Interferons regulate the expression of a large number of genes, with different cellular functions. We investigate the role of interferon-regulated genes in autoimmune diseases and cancer. By isolating different immune cell populations from patients and controls followed by gene expression analyses, we obtain a cell-specific map of their expression. The function of identified interferon-regulated genes is investigated both in vitro, using techniques such as lentiviral CRISPR/Cas9 and shRNA, and in vivo using experimental models. In addition, we use genome-wide CRISPR/Cas9 libraries in cancer cells to identify genes involved in metastasis and drug response. We aim to identify interferon-regulated genes that have the potential to be targets for new drugs and that are involved in the pathogenic mechanisms of autoimmune diseases and cancer respectively. This project is led by docent Alexander Espinosa.
Cutaneous T-cell lymphoma is a rare type of lymphoma that mainly affects the skin. Most patients with cutaneous T-cell lymphoma have a low-grade disease, but for largely unknown reasons, approximately 10-15% over time develop an aggressive form with high mortality. Because the lymphoma is localized to the skin, it can be easily followed with inspection and biopsies, in which the cancer cells and the patient's anti-lymphoma immune response can be examined. A specific focus of ours are the so-called natural killer cells, natural killer cells (NK cells) and their role in the body's defense against cancerous cells. We are also investigating possible immune mechanisms and tumor characteristics that control cancer development in patients with autoimmunity, including dermatomyositis and systemic lupus erythematosus. These projects are led by docent Hanna Brauner.
The results from our studies will lead to cellular and molecular understanding of both autoimmune and cancer diseases. The goal is to use the information to develop prevention, new diagnostics and treatment for these diseases.