TGF-β regulated leukemia cell susceptibility against NK targeting through the down-regulation of the CD48 expression

Chin Han Huang, Yi Jen Liao, Tzeon Jye Chiou, Hsin Ting Huang, Yen Hsi Lin, Yuh Ching Twu

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Transforming growth factor-β (TGF-β) is known to function as a dual role regulatory cytokine for being either a suppresser or promoter during tumor initiation and progression. In solid tumors, TGF-β secreted from tumor microenvironment acts as a suppresser against host immunity, like natural killer (NK) cells, to favor tumor evasion. However, besides solid tumors, the underlying mechanism of how TGF-β regulates leukemogenesis, tumor progression, immunoediting, and NK function is still not clear in detail. In this study, we found that TGF-β induced leukemia MEG-01 and U937 cells to become less sensitive to NK-92MI targeting by down-regulating CD48, a ligand for NK activating receptor 2B4, but not down-regulating other tumor-associated carbohydrate antigens (TACAs). In CD48-knockdown cells, cells responding to NK-92MI targeting displayed a phenotype of less NK susceptibility and cell conjugation. On the other hand, when NK cells were treated with TGF-β, TGF-β suppressed NK recognition, degranulation, and killing activity in time-dependent manner by regulating ICAM-1 binding capacity instead of affecting expressions of activating and inhibitory receptors. Taken together, both leukemia cells and immune NK cells could be regulated by TGF-β through suppressing leukemia cell surface CD48 to escape from host surveillance and down-regulating NK cell surface ICAM-1 binding activity to impair NK functions, respectively. Our results suggested that TGF-β had effect in leukemia similar to that observed in solid tumors but through different regulatory mechanism.

Original languageEnglish
JournalImmunobiology
DOIs
Publication statusPublished - Jan 1 2019

Keywords

  • CD48
  • Immunosurveillance
  • NK cell
  • TGF-β

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Hematology

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