The Role of CMV in Influencing Adaptive NK Cells

Due to their ability to target a wide range of different cancers, natural killer (NK) cells are ideal candidates for immunotherapy. It’s becoming increasingly clear that subsets of NK cells exist that differ in their capacity to lyse targets, produce cytokines, mediate immune memory, proliferate and survive, and thus each subset of NK cells will have a different ability to eliminate cancer. We have identified and characterised several NK cell subsets that expand following cytomegalovirus (CMV) reactivation in patients receiving haematopoietic stem cell transplants (HSCT) for the treatment of various haematological malignancies. These NK cells, which can also be found in healthy donors, have enhanced functional potential and survival capacity. Interestingly, CMV, a common infection in transplant recipients, has been associated with reduced risk of leukaemic relapse in recipients of haematopoietic stem cell transplantation (HSCT). Collectively, these NK cell subsets that expand in the context of CMV infection are termed adaptive NK cells. Multi-parameter flow cytometry has been used extensively to characterise the phenotype and function of these cells in both transplant recipients and healthy donors. Due to their enhanced functional potential we predicted that adaptive NK cells may have increased ability to eliminate tumours. We are currently developing multi-parameter panels to determine which subsets of adaptive NK cells are the most effective at eliminating tumours and these findings will be used to develop novel immune-based therapies to treat patients in the clinic. 

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