3 years ago

Strategies to activate NK cells to prevent relapse and induce remission following hematopoietic stem cell transplantation.

Peter Parham, Jeffrey S Miller, Sarah Cooley
Natural Killer (NK) cells are lymphocytes of innate immunity that respond to virus infected and tumor cells. After allogeneic transplantation, NK cells are the first reconstituting lymphocytes, but are dysfunctional. Manipulating this first wave of lymphocytes could be instrumental in reducing the 40% relapse rate following transplantation with reduced intensity conditioning. NK cells express numerous activating and inhibitory receptors. Some recognize classical or non-classical HLA class I ligands, others recognize class I-like ligands or unrelated ligands. Dominant in the NK cell transplant literature are killer cell immunoglobulin-like receptors (KIR), encoded on chromosome 19q. Inhibitory KIR recognition of cognate HLA class I ligand is responsible for NK cell education, which makes them tolerant of healthy cells, but responsive to unhealthy cells having reduced expression of HLA class I. KIR A and KIR B are functionally distinctive KIR haplotype groups that differ in KIR gene content. Allogeneic transplant donors having a KIR B haplotype and lacking a recipient HLA-C epitope provide protection against relapse from acute myeloid leukemia (AML). Cytomegalovirus (CMV) infection stimulates and expands a distinctive NK cell population that expresses the NKG2C receptor and exhibits enhanced effector functions. These adaptive NK cells display immune memory and methylation signatures like CD8 T cells. As potential therapy, NK cells, including adaptive NK cells, can be adoptively transferred with, or without, agents such as IL-15 that promote NK cell survival. Strategies combining NK cell infusions with CD16-binding antibodies or immune engagers could make NK cells antigen specific. Together with checkpoint inhibitors, these approaches have considerable potential as anti-cancer therapies.

Publisher URL: http://doi.org/10.1182/blood-2017-08-752170

DOI: 10.1182/blood-2017-08-752170

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.