Nature journal: unveiling new secrets of NK cells, promising to develop immunotherapy targeting cancer cells

August 28, 2019 / bioun / - natural killer (NK) cells in your immune system recognize and attack two main dangerous cells - cells infected by virus and cells affected by cancer When NK cells see cancer cells, they kill them (naturally) A major research focus is to determine how NK cells do this One way NK cells look at cancer is to recognize mutated DNA fragments made by the human leukocyte antigen (HLA) gene In fact, there are two types of HLA genes HLA group 1 genes are responsible for the task of producing proteins that display cell DNA for detection and evaluation However, although HLA class 1 genes can help to recognize the bad molecules in human cells, HLA class 2 genes can help the body to mark and lock in the invaders from outside, so as to gather antibodies against bacteria, etc Photo source: Nature Immunology so, why do recent studies show that patients with cancer cells characterized by high expression of hla-2 proteins have better prognosis? Of course, hla-1 antigens can make NK cells attack tumor tissue, but unlike hla-2 antigens, which interact with NK cells, right? Wrong A recent study published by the University of Colorado (Cu) cancer center in the journal Nature Immunology shows that NK cells do interact with hla-2 molecules The findings may help researchers better use the immune system to fight cancer, on the other hand, they may also help to quell the immune system's attack on healthy tissues under certain autoimmune conditions "It is understood that NK cells interact with HLA group 1 molecules but not HLA group 2 molecules The mechanism of HLA 2 interaction with NK cells has changed our view of NK cell biology "Dr Paul Norman, co-author of the study, is an associate professor at the Cu cancer center, the Department of personalized medicine, the Department of Microbiology and immunology at the school of medicine Collaborators at the German Center for infection research screened proteins produced by the HLA 2 gene to see if there was one that activated NK cells "This is called ligand screening - testing many potential ligands to see what sticks together However, since the fact that hla-2 molecules do not interact with NK molecules has been confirmed, no one has studied this They are smart enough to pay attention to the problem when others don't "Norman said Specifically, the team found that a HLA type 2 HLA called hla-dp401 does activate NK cells, and hla-dp401 is one of the most common variants (called alleles) found in Europe "The problem is that not all of these HLA 2 molecules can be recognized by NK cells HLA is polymorphic Different individuals have different types of HLA The next step is to determine which patients have the right combination of HLA 2 and NK cells, and then we may learn to engineer NK cells to interact with HLA class 2 molecules "Norman said Norman's ongoing research hopes to further clarify the mechanism of interaction between hla-2 genes and NK cells "In the end, it could be another way to direct immune cells to cancer and away from healthy tissue," Norman said "Reference: Annika niehrs et al, a subset of HLA-DP molecules serve as lives for the natural cytoxicity receptor NKp44, Nature Immunology (2019) Doi: 10.1038/s41590-019-0448-4