Heme oxygenase-1 inhibits the cytotoxicity of natural killer cells to acute myeloid leukemia by downregulating human leukocyte antigen-C

  • Cytotherapy. 2023 Mar 6;S1465-3249(23)00037-3. doi: 10.1016/j.jcyt.2023.02.001.
Cheng Feng  1 ,  Tianzhuo Zhang  1 ,  Chengyun Pan  1 ,  Qian Kang  1 ,  Li Wang  1 ,  Xin Liu  1 ,  Qin Shang  1 ,  Siyu Chen  1 ,  Tianzhen Hu  1 ,  Jishi Wang  2
Affiliations
  • 1. Clinical Medicine College of Guizhou Medical University, Guiyang, China; Department of Hematology, Affiliated Hospital of Guizhou Medical University, Guizhou Province Institute of Hematology, Guizhou Province Laboratory of Hematopoietic Stem Cell Transplantation Centre, Guiyang, China.
  • 2. Clinical Medicine College of Guizhou Medical University, Guiyang, China; Department of Hematology, Affiliated Hospital of Guizhou Medical University, Guizhou Province Institute of Hematology, Guizhou Province Laboratory of Hematopoietic Stem Cell Transplantation Centre, Guiyang, China. Electronic address: [email protected].
PMID: 36890092 DOI: 10.1016/j.jcyt.2023.02.001
Abstract

Background aims: Recently, immune escape has been considered as a factor leading to relapse of acute myeloid leukemia (AML). In our previous study, heme oxygenase 1 (HO-1) proved to play an essential role in the proliferation and drug resistance of AML cells. In addition, recent studies by our group have shown that HO-1 is involved in immune escape in AML. Nevertheless, the specific mechanism by which HO-1 mediates immune escape in AML remains unclear.

Methods: In this study, we found that patients with AML and an overexpression of HO-1 had a high rate of recurrence. In vitro, overexpression of HO-1 attenuated the toxicity of natural killer (NK) cells to AML cells. Further study indicated that HO-1 overexpression inhibited human leukocyte antigen-C and reduced the cytotoxicity of NK cells to AML cells, leading to AML relapse. Mechanistically, HO-1 inhibited human leukocyte antigen-C expression by activating the JNK/c-Jun signaling pathway.

Results: In AML, HO-1 inhibits cytotoxicity of NK cells by inhibiting the expression of HLA-C, thus causing immune escape of AML cells.

Conclusions: NK cell-mediated innate immunity is important for the fight against tumors, especially when acquired immunity is depleted and dysfunctional, and the HO-1/HLA-C axis can induce functional changes in NK cells in AML. Anti-HO-1 treatment can promote the antitumor effect of NK cells and may play an important role in the treatment of AML.

Keywords
acute myeloid leukemia; heme oxygenase-1; human leukocyte antigen-C; natural killer cells.
Products