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

研究成果: 雜誌貢獻文章

摘要

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.
原文英語
頁(從 - 到)138-151
頁數14
期刊Immunology and Cell Biology
98
發行號2
DOIs
出版狀態已發佈 - 二月 1 2020

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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    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