New research reveals how the immune system turns a blind eye to cancer cells

T cells play a huge role in our immune system against cancer cells that can lead to cancer in the body Phagocytes and B cells recognize changes in these cancerous cells and activate T cells, then initiate a complete destruction process This works in many cases - unless cancer cells mutate to form a good camouflage, so they can escape the immune system without detection In a new study, researchers from the universities of Freiburg and Hannover Leibniz in Germany described a key protein in this process by using biophysical, biochemical and immunological methods Based on these new insights, they hope to develop drugs that specifically intervene in this activation mechanism In the future, they may improve existing cancer treatments that rely on so-called immune checkpoint inhibitors The relevant research results were published in the Journal of science advances on January 31, 2020, and the title of the paper is "molecular mechanism of SHP2 activation by PD-1 stimulation" The corresponding authors of the paper are professor Maja banks-k ö HN of the University of Freiburg and Professor Teresa carlomagno of the University of Hanover Leibniz Picture from science advanced, 2020, DOI: 10.1126/sciadv.aay4458 Immunocheckpoint inhibitors are therapeutic antibodies that work by binding to receptors on the surface of T cells These receptors are proteins on the surface of T cells called immune checkpoint receptors, including PD-1 Together, these receptors and their triggered signaling pathways block immune responses in healthy humans This regulatory mechanism prevents inflammatory symptoms from persisting for too long and out of control - symptoms of inflammation that are not inhibited include redness, swelling, and fever Cancer cells use inflammatory mechanisms to make the body helpless as cells proliferate Through cell culture and interaction studies, the researchers found that a signaling protein called SHP2 in T cells, activated by signals from cancer cells, binds to PD-1 at two specific sites It is this dual binding of SHP2 that promotes camouflage and completely shuts down the immune cell response Antibodies that block immune checkpoints such as PD-1 have been approved for the treatment of skin melanoma and lung cancer, and extend the life of patients However, many patients also suffer from autoimmune response "Drugs that block the binding between SHP2 and PD-1 may be used in the future to reduce side effects and support or replace antibody therapy," banks-k ö HN said Banks-k ö HN and Wolfgang schamel, co-author of the paper and professor of Freiburg University, studied the immune response of B cells and T cells by modifying SHP2 molecules, and tested their predictions based on the crystal structure and magnetic resonance analysis of the carlomagno research team Their data accurately show how and where SHP2 binds to PD-1, thus revealing the potential target areas of the drug "In our ongoing research project, the next step is to decipher the PD-1 signaling pathway, in other words, the location of proteins in this signaling pathway in the cell, where they bind, and the effective time range of the signal," banks-k ö HN said reference material: 1.M Marasco et al Molecular mechanism of SHP2 activation by PD-1 stimulation Science Advances, 2020, doi:10.1126/sciadv.aay4458.