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Review
, 21 (10), 93

The Role of Natural Killer Cells as a Platform for Immunotherapy in Pediatric Cancers

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Review

The Role of Natural Killer Cells as a Platform for Immunotherapy in Pediatric Cancers

Miriam Santiago Kimpo et al. Curr Oncol Rep.

Abstract

Purpose of review: We aim to review the most recent findings in the use of NK cells in childhood cancers.

Recent findings: Natural killer cells are cytotoxic to tumor cells. In pediatric leukemias, adoptive transfer of NK cells can bridge children not in remission to transplant. Interleukins (IL2, IL15) can enhance NK cell function. NK cell-CAR therapy has advantages of shorter life span that lessens chronic toxicities, lower risk of graft versus host disease when using allogeneic cells, ability of NK cells to recognize tumor cells that have downregulated MHC to escape T cells, and possibly less likelihood of cytokine storm. Cytotoxicity to solid tumors (rhabdomyosarcoma, Ewing's sarcoma, neuroblastoma) is seen with graft versus tumor effect in transplant and in combination with antibodies. Challenges lie in the microenvironment which is suppressive for NK cells. NK cell immunotherapy in childhood cancers is promising and recent works aim to overcome challenges.

Keywords: Adoptive cell therapy; CAR-NK; Natural killer cells; Tumor microenvironment.

Conflict of interest statement

Miriam Santiago Kimpo, Bernice Oh, and Shawn Lee declare they have no conflict of interest.

Figures

Fig. 1
Fig. 1
NK cell activation programs result from the integration of multiple activating and inhibitory signals that vary depending on the nature of the interacting cells. These signals involve ITAM (immunoreceptor tyrosine-based activation motif)-bearing molecules and other stimulatory receptors and adhesion molecules, as well as ITIM-bearing inhibitory receptors. Some human (left) and mouse (right) receptor-ligand interactions are depicted here, to illustrate the combinatorial nature of the NK cell interaction repertoire. Cytokines, chemokines, and their receptors are not shown, but are also crucial for the regulation of NK cell functions. Inhibitory receptors are in blue; 2B4, which can act as an activating or an inhibitory molecule, is in gray; other receptors are in green. Vertical lines indicate the receptor-ligand pairs conserved between mice and humans, which consist either of real orthologs (for example, human and mouse NKp46) or examples of convergent evolution (for example, KIR and Ly49). KIR, killer immunoglobulin-like receptors; LIR, immunoglobulin-like transcript; LAIR, leukocyte-associated immunoglobulin-like receptor; SIGLEC, sialic acid binding immunoglobulin-like lectins; KLRG-1, killer cell lectin-like receptor G1; NKR-P1, NK cell receptor protein 1; HLA, human leukocyte antigen; LLT, lectin-like transcript; CRTAM, class I restricted T cell-associated molecule; Necl-2, nectin-like 2; Tactile (also known as CD96), T cell-activated increased late expression; CEACAM1, carcinoembryonic antigen-related cell adhesion molecule 1; PILR, paired immunoglobulin-like type 2 receptor; NTB-A, NK-T-B antigen; CRACC, CD2-like receptor-activating cytotoxic cell; VCAM-1, vascular cell adhesion. Reproduced from Vivier E, et al. “Functions of natural killer cells.” Nat Immunol. 2008 May;9 [3]:503-10, by permission from Springer Nature, ©2008

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