• Title/Summary/Keyword: NKG2D lignads

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Differential Effects of Transforming Growth Factor-β on NKG2D Ligands Expression and NK Cell-mediated Immune Responses in Primary and Metastatic Colon Cancer (원발성 및 전이성 대장암에서 TGF-beta가 NKG2D 리간드 발현과 NK 세포 매개 면역반응에 미치는 영향)

  • Eun-Jung Yun;Yu-Rim Kim;Seong Jun Park;Sang-Yull Lee;Jaeho Bae
    • Journal of Life Science
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    • v.33 no.2
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    • pp.149-157
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    • 2023
  • Transforming growth factor-β (TGF-β) is a multifunctional cytokine that affects not only the survival and growth of cancer cells but also the activity of immune cells. Although it has been generally accepted that cancer cell-derived TGF-β could promote the survival and growth of early cancer cells and have immunosuppressive roles, it has been known that TGF-β has differential effects according to the type or stage of cancer cells. Therefore, it is hard to clearly define its role in cancer progression and immune responses. This study investigated the effects of TGF-β signaling on the expression of five NKG2D ligands and the NK cell-mediated anticancer immune response in the primary colon cancer cell line KM12C and its two metastatic cell lines, KM12SM and KM12L4A. At the surface protein level, exogenous TGF-β decreased the expression of MICA, MICB, ULBP1, and ULBP2, and galunisertib increased the expression of MICA, MIAB, ULBP1, ULBP2, and ULBP3 in KM12C. However, KM12SM and KM12L4A showed no significant changes in the expression of NKG2DLs after treatment with TGF-β or galunisertib. TGF-β signaling inhibition via galunisertib improved the NK cell-mediated anticancer immune response against KM12C but did not show a significant response to KM12SM and KM12L4A. Therefore, the suppression of TGF-β signaling could improve the NK cell-mediated anticancer immune response against KM12C. However, an increase in NKG2DLs expression and an enhanced NK cell-mediated cancer immune response is hard to expect due to the alteration of TGF-β signaling in KM12SM and KM12L4A.