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Reconstitution of innate immunity in B-chronic lymphocytic leukemia: time to reconsider the possibilities

Leukemia volume 17, pages 1945–1947 (2003)Cite this article

In this issue of Leukemia, Guven et al1 demonstrate an in vitro system that supports an expansion of both natural killer (NK) and natural killer-like (NKT) cells from patients with B-chronic lymphocytic leukemia (B-CLL). Given the inherent immunodeficiencies found in both early- and late-stage B-CLL and the exacerbation of those deficits with newer effective therapies, the work by Guven et al reported here may profound implications for B-CLL patients.

The immune system can be broadly divided into innate and adaptive arms, which together make up an integrated system of host defenses. It is now clear that innate immunity is critically important for jump starting and regulation of adaptive immunity.2 Both NK and NKT cells are known to be important in the innate immunity of the healthy host. NK cell presence was initially inferred from their capacity to spontaneously kill certain tumor targets. NK function does not require prior deliberate immunization of the host with the target cells. The assay to detect natural killing is most often an NK-sensitive target labeled by incubation with sodium [51Cr] chromate. For human NK cells, the standard tumor target is K562 a cell line derived from an erythroleukemic lineage. Morphologically, NK cells are featured as large lymphocytes containing azurophilic granules and have been designated as the large granular lymphocyte.3 However, even small, agranular lymphocytes may demonstrate similar cytolytic activity.4 NK cells possess interleukin (IL)-2 receptors,5 so exposure to IL-2 results in a significant expansion of size and function and has been designated as lymphokine-activated killer (LAK) cells. Other signal surface markers for NK cells include CD56, a 140 kDa glycoprotein that is called NKH19;6 CD2, which is also present on T cells; and CD16, an Fc receptor.7 CD16 is associated with the ζ chain of the TCR-CD3 complex, which is involved in the signal transduction triggered by antibodies binding to CD16 and leads to activation of the cell. Relevant to Guven et al‘s work, NK cells and LAK cells have been found to be of some limited use in the immunotherapy of cancer.8 However, NK cells may play a role in host defense against the emergence of malignancies,9 in response to infection10 and could have a role in the pathogenesis of autoimmune disorders such as rheumatoid arthritis.11 Since CLL patients have problems with increased incidence of infection,12 autoimmune disorders13 and increased risk of skin and solid tumors, these cells are likely playing a role in the well being of CLL patients.

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  1. Division of Hematology, Mayo Clinic, Rochester, MN, USA

    Y K Lee & N E Kay

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Lee, Y., Kay, N. Reconstitution of innate immunity in B-chronic lymphocytic leukemia: time to reconsider the possibilities. Leukemia 17, 1945–1947 (2003). https://doi.org/10.1038/sj.leu.2403082

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