What is the role of NK cell activation in immunotherapeutic targeting in pediatric oncology?

Updated: Mar 20, 2018
  • Author: Crystal L Mackall, MD; Chief Editor: Jennifer Reikes Willert, MD  more...
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Answer

Answer

Natural killer (NK) cells are lymphoid cells that are part of the innate immune system because they do not express clonotypic receptors or mediate immunologic memory. However, they are potent mediators of antitumor effects because they identify and kill tumor cells in the absence of inflammatory signals and can directly reject tumors.

NK cell activation is a complex process, with interactions among various activating and inhibitory NK cell receptors and various ligands determining whether NK cells activate and kill targets. [26]

The major NK cell inhibitory receptors are the killer immunoglobulinlike receptors (KIRs), which are expressed on the surface and inactivate the NK cell when it encounters a cell that expresses self-major histocompatibility complex (MHC) class I. Activating receptors include NKG2D, which binds MHC class I chain-related molecule A or B (MICA or MICB) on tumor cells, and Fc receptors, which bind the Fc region of antibody molecules.

Several clinical trials have shown that adult patients with AML who underwent bone marrow transplant and were mismatched for NK cell–KIR and MHC displayed improved survival. [27] This success appears to be contingent on using a T-cell–depleted transplant, perhaps because of the absence of immunosuppressive agents that may interfere with the natural killer cell–mediated effects.

A phase II trial through the Children’s Oncology Group is currently exploring the efficacy of allogeneic NK cell–KIR mismatched transplants in children with relapsed, refractory, or newly diagnosed AML, and recruitment is ongoing (see Clinicaltrials.gov).


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