NK cells modulation in hematological malignancies

Hematological malignancies treatment improved over the last years resulting in increased achievement of complete or partial remission, but unfortunately high relapse rates are still observed, due to remaining minimal residual disease (MRD). Therefore, sustainment of long-term remission is crucial, using either drug maintenance treatment or by boosting or prolonging an immune response. Immune system has a key role in tumor surveillance. Nonetheless, tumor cells evade the specific T-lymphocyte mediated immune surveillance using many mechanisms but especially by the down-regulation of the expression of HLA class I antigens. In theory, these tumor cells lacking normal expression of HLA class I molecules should be destroyed by natural killer (NK) cells, according to the missing-self hypothesis. NK cells, at the frontier of innate and adaptive immune system, have a central role in tumor cells surveillance as demonstrated in the setting of allogenic stem cell transplantation. Nevertheless, tumors develop various mechanisms to escape from NK innate immune pressure. Abnormal NK cytolytic functions have been described in many hematological malignancies. We present here various mechanisms involved in the escape of hematological malignancies from NK cells surveillance, i.e. NK cells quantitative and qualitative deficiency by increased inhibitory signaling or decreased activating stimuli. Abnormal NK functions could be related to cytokine secretion by tumor cells, reactive oxygen species (ROS), inhibitory tumor cell surface molecules, or even RNA transfer during cell-cell contact between NK and target cells.