Granzyme B and perforin produced by SEC2 mutant-activated human CD4 + T cells and CD8 + T cells induce apoptosis of K562 leukemic cells by the mitochondrial apoptotic pathway.

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  • Author(s): Zhang G;Zhang G; Zheng G; Zheng G; Jiang F; Jiang F; Wu T; Wu T; Wu L; Wu L
  • Source:
    International journal of biological macromolecules [Int J Biol Macromol] 2021 Nov 01; Vol. 190, pp. 284-290. Date of Electronic Publication: 2021 Sep 04.
  • Publication Type:
    Journal Article
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: Netherlands NLM ID: 7909578 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0003 (Electronic) Linking ISSN: 01418130 NLM ISO Abbreviation: Int J Biol Macromol Subsets: MEDLINE
    • Publication Information:
      Publication: Amsterdam : Elsevier
      Original Publication: Guildford, Eng., IPC Science and Technology Press.
    • Subject Terms:
      Apoptosis*; CD4-Positive T-Lymphocytes/*immunology ; CD8-Positive T-Lymphocytes/*immunology ; Enterotoxins/*genetics ; Granzymes/*metabolism ; Leukemia/*pathology ; Mitochondria/*metabolism ; Perforin/*metabolism; Cell Proliferation ; Humans ; K562 Cells ; Leukemia/immunology ; Lymphocyte Activation ; Mutation/genetics ; Receptors, Antigen, T-Cell/metabolism
    • Abstract:
      Staphylococcal enterotoxin C2 (SEC2), a classical representative of superantigens, activates T cells that produce massive cytokines. This characteristic makes SEC2 a promising candidate drug for cancer immunotherapy. Previous study showed that ST-4, a SEC2 mutant, enhanced recognition of mouse T-cell receptor Vβ regions, and activated the increased number of T cells that produced more cytokines. However, the underlying molecular mechanism for stimulation of human peripheral blood mononuclear cells (PBMCs) and antitumor effect on human tumor cells remains unknown. Herein, we showed that ST-4 significantly activated TCR Vβ 12, 13A, 14, 15, 17, and 20 CD4 + and CD8 + T cells, which produced substantial amounts of granzyme B and perforin. These cytokines exhibited antitumor effect on K562 cells by promoting apoptosis and inducing S-phase cell cycle arrest. Conversely, the granzyme B inhibitor or perforin inhibitor significantly weakened antitumor effect of ST-4, accompanied by a decrease of cleaved proapoptotic BAX and cytochrome c, and an increase of antiapoptotic BCL2. Taken together, these data suggest that granzyme B and perforin produced by ST-4-activated CD4 + T cells and CD8 + T cells play a pivotal role in inducing K562 cell apoptosis by the mitochondrial apoptotic pathway, and support ST-4 as a potential candidate for cancer immunotherapy.
      (Copyright © 2021. Published by Elsevier B.V.)
    • Contributed Indexing:
      Keywords: Granzyme B; Perforin; Staphylococcus enterotoxin C2
    • Accession Number:
      0 (Enterotoxins)
      0 (Receptors, Antigen, T-Cell)
      126465-35-8 (Perforin)
      EC 3.4.21.- (Granzymes)
    • Publication Date:
      Date Created: 20210907 Date Completed: 20211215 Latest Revision: 20211215
    • Publication Date:
      20240829
    • Accession Number:
      10.1016/j.ijbiomac.2021.08.225
    • Accession Number:
      34492245