UNASSIGNED: Natural killer (NK) cells are most efficient if their targets do not express self MHC class I, because NK cells carry inhibitory receptors that interfere with activating their cytotoxic pathway. Clinicians have taken advantage of this by adoptively transferring haploidentical NK cells into @entity1 to mediate an effective graft-versus- @entity1778 response. With a similar rationale, antibody blockade of MHC class I-specific inhibitory NK cell receptors is currently being tested in clinical trials. Both approaches are challenged by the emerging concept that NK cells may constantly adapt or "tune" their responsiveness according to the amount of self MHC class I that they sense on surrounding cells. Hence, these therapeutic attempts would initially result in increased killing of @entity5 cells, but a parallel adaptation process might ultimately lead to impaired antitumor efficacy. We have investigated this question in two @entity19 models: inhibitory receptor blockade in vivo and adoptive transfer to MHC class I-disparate hosts. We show that changed self-perception via inhibitory receptors in mature NK cells reprograms the reactivity such that tolerance to healthy cells is always preserved. However, reactivity against @entity5 cells lacking critical MHC class I molecules (missing self-reactivity) still remains or may even be increased. This dissociation between activity against healthy cells and @entity5 cells may provide an answer as to why NK cells mediate graft-versus- @entity1778 effects without causing @entity2132 and may also be utilized to improve immunotherapy. Cancer Immunol Res; 4(2); 1-11.   2015 AACR.

Retuning of XXXX NK Cells after Interference with MHC Class I Sensing Adjusts Self-Tolerance but Preserves Anticancer Response.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity19 :: ('10090', 'Species') :: ['mouse'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancer'] @entity1778 :: ('MESH:D007938', 'Disease') :: ['leukemia'] @entity2132 :: ('MESH:D006086', 'Disease') :: ['graft-versus-host disease']
@entity19 :: (10090,Species) :: ['Mouse']
