Protein landscape on cancer cells mapped with new technology

Researchers at IGP have demonstrated a mechanism for how cancer killing immune cells called CAR- T cells sometimes are prematurely exhausted and fail to kill the cancer cells. They also present new CAR-T cells against brain tumours that lack this unwanted exhaustion feature. The future aim is to use these CAR-T cells to treat brain cancer. The study has been published in the journal Nature Communications.

Researchers at IGP have developed a new method to find mutations in brain tumours in children. They could also show that the mutations identified by them changes how cancer cells respond to a cancer drug. These findings could lead to better diagnostics and more individualized treatment of children with brain tumours.

The blood cancer form acute myeloid leukemia (AML) is an extremely heterogeneous disease where disease development and therapeutic approach are mainly dictaded by genetic alterations in the malignant cells. In a recent study from IGP, the researchers show that a certain type of abnormality in the gene RUNX1 affects the classification of patients with AML and thereby the optimal therapy selection.

Many studies have linked obesity to an increased risk of cancer, but most have not differentiated the risks between men and women. In a new study, researchers from IGP take a closer look at this connection. The investigators report that both overall fat accumulation and fat distribution in different parts of the body confer different cancer risks depending on biological sex. Additionally, the risks vary across cancer types. The results are published in the journal Cancer Cell.

Women who used combined contraceptive pills were at greater risk of developing depression than women who did not, according to a new study from IGP. Contraceptive pills increased women’s risk by 73 per cent during the first two years of use.

A new study from IGP shows that a higher body mass index (BMI) increases the risk of five different rheumatic diseases; rheumatism, osteoarthritis, gout, psoriatic arthritis and inflammatory spondylitis. The researchers were also able to see that BMI was a stronger risk factor for women compared to men when it came to the diseases gout and psoriatic arthritis. The study is presented in the scientific journal Arthritis and Rheumatology.

Researchers from IGP have developed a method that helps immune cells exit from blood vessels into the tumour and kill cancer cells. The aim is to improve treatment of aggressive brain tumours. The study has been published in the journal Cancer Cell.

In a large international project jointly led by Uppsala University and the Broad Institute, more than 30 research teams have together surveyed and analysed the genomes of 240 mammal species. The results, now published in 11 articles in the journal Science, show mutations that can cause disease. Karin Forsberg Nilsson and Ananya Roy at IGP have participated in one of the papers, where they have identified mutations associated with the cancer type medulloblastoma.

A recent study by IGP researchers shows that the protein IRAK3 reduces the effect of immunotherapy against cancer. One way of improving the therapy response could be to reduce the amount the IRAK3 with drugs that target the protein.  

A new study by researchers at IGP shows that men who have a neurodevelopmental disorder, such as autism and ADHD, also have a slightly increased risk of testicular cancer, or seminoma.

When the human remains found on board the warship Vasa were investigated, it was determined that they were all male. New research now shows that one of the skeletons is actually from a woman.

Researchers at IGP have identified a combination of two types of immune cells that characterise certain cancer forms. This combination can be used to provide disease prognosis and predict treatment response to immunotherapy. The findings are presented in a new study in the journal eBioMedicine.

Researchers at IGP have discovered a new cell subtype in the lymphatic vessels that interacts with immune cells in lymphatic malformations. This newly discovered interplay between the immune system and the lymphatic system could be used to treat diseases with lymphatic malformations.

Researchers at IGP have identified a protein involved in regulating leakage from blood vessel. Its role in controlling cell–cell contacts, challenges prior knowledge and opens up new avenues for future therapeutic development in diseases involving vessel leakage and tissue swelling.

Men are at an increased risk of a severe bout of COVID-19 compared to women. Researchers at IGP have now shown that this may be due to loss of the Y chromosome in part of their white blood cells. The findings could eventually be used to assess the risk of developing severe COVID-19 and perhaps to improve treatment.

The malignant brain tumour type medulloblastoma can become resistant to therapy which can cause relapse. Researchers at IGP have discovered a certain protein that among other things makes tumour cells resting and insensitive to radiation treatment. The research group hopes that the results could eventually lead to better treatments for children that have the highest risk to develop relapses.

Single periods of sun exposure or radiation therapy to the skin likely pose a minimal risk of skin cancer. This is suggested in a study from IGP where the researchers have shown that pigment-producing cells in the skin can skin can tolerate long-term exposure of genetic injuries by changing between different degrees of maturity.

Researcher at IGP have developed a new tool that enables the visualisation where drugs bind to human proteins. The highly sensitive technique can be used in searches for compounds with specificity for particular target proteins. It could be used in drug discovery processes or to establish the suitability of a given drug regime before therapy selection.

Using state of the art techniques, researchers from Uppsala University have shown that the metabolism in patients with type 2 diabetes and prediabetes was much more disturbed than previously known, and that it varied between organs and with the severity of the disease. The study, which is a collaboration with Copenhagen University and AstraZeneca, among others, has been published in the journal Cell Reports Medicine.

In a large international study, researchers at IGP have identified DNA regions that are associated with physical activity or leisure screen time. The findings confirm that physical activity is beneficial for health and suggest that a more sedentary lifestyle can be due to how the muscles respond to exercise.

Blood coagulation and blood clot formation are relevant for the disease cerebral cavernoma, CCM. Therefore, antithrombotic therapy may be beneficial for cavernoma patients. This is shown in a new study from IGP.

Loss of the Y chromosome in blood cells of men is associated with disease and mortality, but no clear causal relationship has previously been identified. Now, researchers from IGP show in an international study in the journal Science that loss of the Y chromosome in white blood cells causes development of fibrosis in the heart, impaired heart function and death from cardiovascular diseases in men.

Researchers at IGP have developed a new method to detect proteins with high specificity and sensitivity that could be use in future diagnostic analyses of patient samples.

A new study from IGP show that oral contraceptives and also hormone replacement therapy at menopause increase the risk of stroke. The increased risk was largest during the first year of treatment, after which it declined. The study, which is now published in the journal Stroke, is based on data from more than a quarter of a million women from the database UK Biobank.

Although some rare variants can significantly increase the risk of disease for a few individuals, the majority of the genetic contribution to common diseases is due to a combination of many common genetic variants with small effects. This is shown by researchers at IGP and other departments at Uppsala University in a new comprehensive study published in the journal Nature Communications.

Researchers at IGP have detected different subgroups of the brain tumour form glioblastoma, where the cancer cells’ properties depend on which cell type they originate from. The used analysis method could also separate glioblastoma patients with significant differences in survival. The findings open up for identifying specific therapeutic targets for the new subgroups of glioblastoma.

Immunotherapy is increasingly becoming a successful way to treat cancer. Researchers at IGP have now developed armed CAR-T cells that reinforce the immune defence against cancer and that could increase the possibilities to successfully treat solid tumours. The study has been published in the journal Nature BioMedical Engineering.

In the condition known as cavernoma, lesions arise in a cluster of blood vessels in the brain, spinal cord or retina. Researchers at IGP now show in a new study that white blood cells and protein structures associated with the immune response infiltrate the vessel lesions. The findings support that inflammation has a role in the development of cavernoma and indicate a potential biomarker for the disease.  

In recent years, great advances have been made in the development of new, successful immunotherapies to treat cancer. Two types of targeted immunotherapies that have revolutionised areas of cancer care are CAR T-cell therapy and antibody treatments. However, there are still significant challenges in the identification of cancer cell surface proteins that function as targets for immunotherapies. Mattias Belting, professor at Lund University and senior consultant at Skåne University Hospital, and guest professor at IGP, is well on the way and his group’s findings are now published in the journal PNAS.

CRISPR-Cas9, the “genetic scissors”, creates new potential for curing diseases; but treatments must be reliable. In a new study, researchers have discovered that the method can give rise to unforeseen changes in DNA that can be inherited by the next generation. These scientists therefore urge caution and meticulous validation before using CRISPR-Cas9 for medical purposes.

Researchers at IGP have developed a technology that allows studies of DNA profiles in archived tissue samples. The technology permits investigators to better understand regulation of gene activity in cancer and precision medicine.

In the blood cancer type acute myeloid leukemia, it is common that patients relapse some time after treatment. Researchers from IGP have in a new study identified genes that seem to be associated with the risk of relapse. The findings may form the basis for new treatment strategies and contribute to better survival for patients with acute myeloid leukemia.