Macrophages protect mycoplasma-infected chronic myeloid leukemia cells from natural killer cell killing

Qing Wei Winnie Choo, Ricky Abdi Gunawan Koean, Shu Chun Chang, Wee Joo Chng, Ming Chun Chan, Wilson Wang, Jun Zhi Er, Jeak Ling Ding

Research output: Contribution to journalArticle

Abstract

Macrophages (Mϕ) have been reported to downmodulate the cytotoxicity of natural killer (NK) cell against solid tumor cells. However, the collaborative role between NK cells and Mϕ remains underappreciated, especially in hematological cancers, such as chronic myeloid leukemia (CML). We observed a higher ratio of innate immune cells (Mϕ and NK) to adaptive immune cells (T and B cells) in CML bone marrow aspirates, prompting us to investigate the roles of NK and Mϕ in CML. Using coculture models simulating the tumor inflammatory environment, we observed that Mϕ protects CML from NK attack only when CML was itself mycoplasma-infected and under chronic infection–inflammation condition. We found that the Mϕ-protective effect on CML was associated with the maintenance of CD16 level on the NK cell membrane. Although the NK membrane CD16 (mCD16) was actively shed in Mϕ + NK + CML trioculture, the NK mCD16 level was maintained, and this was independent of the modulation of sheddase by tissue inhibitor of metalloproteinase 1 or inhibitory cytokine transforming growth factor beta. Instead, we found that this process of NK mCD16 maintenance was conferred by Mϕ in a contact-dependent manner. We propose a new perspective on anti-CML strategy through abrogating Mϕ-mediated retention of NK surface CD16.

Original languageEnglish
Pages (from-to)138-151
Number of pages14
JournalImmunology and Cell Biology
Volume98
Issue number2
DOIs
Publication statusPublished - Feb 1 2020

Keywords

  • Chronic infection
  • chronic myeloid leukemia
  • inflammation
  • macrophages
  • maintenance of NK mCD16
  • natural killer cells
  • tumor environment

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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  • Cite this

    Choo, Q. W. W., Koean, R. A. G., Chang, S. C., Chng, W. J., Chan, M. C., Wang, W., Er, J. Z., & Ding, J. L. (2020). Macrophages protect mycoplasma-infected chronic myeloid leukemia cells from natural killer cell killing. Immunology and Cell Biology, 98(2), 138-151. https://doi.org/10.1111/imcb.12309