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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1521939
This article is part of the Research Topic Precision Immunotherapy and Novel Target Discovery in Hematological Malignancy View all 6 articles

Aclacinomycin enhances the killing effect of allogeneic NK cells on acute myeloid leukemia cells by inducing immunogenic cell death

Provisionally accepted
Yongbin Ye Yongbin Ye 1*Ning Liu Ning Liu 2*Yunxin Zeng Yunxin Zeng 3Ziwen Guo Ziwen Guo 1*Xiaojun Xu Xiaojun Xu 3*Xiaobo Wang Xiaobo Wang 3,4*
  • 1 Department of Hematology, Zhongshan Hospital Affiliated to Sun Yat-Sen University, Zhongshan, China
  • 2 Department of Hematology, The 6th Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, China
  • 3 Department of Hematology, Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong Province, China
  • 4 Tianyang People's Hospital of Baise City, Baise, China

The final, formatted version of the article will be published soon.

    Natural killer (NK) cells, which exert spontaneous cytotoxicity against infectious diseases and cancer, also play an important role in leukemia therapy. Despite the success of NKbased therapy in the treatment of myeloid leukemia, the potential use of NK alloreactivity in these hematologic malignancies remains elusive. The aim of the present study, was to investigate whether allogeneic NK cells combined with aclacinomycin (ACM) could enhance anti-leukemic functionality against an acute myeloid leukemia (AML) cell line, and to clarify the underlying mechanism. KG-1α and HL-60 AML cell lines were subjected to different treatments. The effects of different drug combinations on cytotoxicity, cell viability and apoptotic status were examined.The results showed that the combination of ACM (40 nmol/l) and allogeneic NK cells (ratio 20:1) was significantly cytotoxic to AML cells and increased the apoptosis of AML cells, especially after 72 h of treatment. Subsequent analyses revealed that the expression of immunogenic cell death (ICD)-related molecules calreticulin, adenosine triphosphate and high mobility group box 1, as well as NK cell effector production-perforin and granzyme B, was markedly increased in the combination treatment group, suggesting that ACM enhances the anti-leukemic activity of allogeneic NK cells through the ICD pathway. These results demonstrated that allogeneic NK cells had enhanced functional responses when stimulated with ACM in vitro, exhibiting superior effector cytokine production and cytotoxicity compared to the control, which contained conventional NK cells. In conclusion, the present study suggested that the combination of ACM and allogeneic NK cells is a promising therapeutic strategy against AML.

    Keywords: aclacinomycin, allogeneic NK cells, acute myeloid leukemia, immunogenic cell ACM, aclacinomycin, AML, acute myeloid leukemia, ATP, adenosine triphosphate, CCK-8, cell counting kit-8, CRT, Calreticulin, DCs, dendritic cells, DMSO, dimethyl sulfoxide, HMGB1, high mobility group box 1

    Received: 03 Nov 2024; Accepted: 13 Jan 2025.

    Copyright: © 2025 Ye, Liu, Zeng, Guo, Xu and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Yongbin Ye, Department of Hematology, Zhongshan Hospital Affiliated to Sun Yat-Sen University, Zhongshan, China
    Ning Liu, Department of Hematology, The 6th Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, China
    Ziwen Guo, Department of Hematology, Zhongshan Hospital Affiliated to Sun Yat-Sen University, Zhongshan, China
    Xiaojun Xu, Department of Hematology, Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong Province, China
    Xiaobo Wang, Department of Hematology, Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong Province, China

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