ArticleCancer communications (London, England)2021
All-trans retinoic acid induces leukemia resistance to NK cell cytotoxicity by down-regulating B7-H6 expression via c-Myc signaling.
Article in Cancer communications (London, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
6 citing papers in PubMed, 8 citations in OpenAlex.
- Cancer-associated fibroblast heterogeneity and its role in reshaping immunotherapy in solid cancers: potential strategies and clinical promise.Frontiers in cell and developmental biology · 2026Review
- B7 homolog 6 promotes the killing activity of natural killer cells against cervical cancer through the downstream ERK pathway of NKp30.Translational cancer research · 2025Article
- STAT3 in acute myeloid leukemia facilitates natural killer cell-mediated surveillance.Frontiers in immunology · 2024Article
- Interleukin-2 is required for NKp30-dependent NK cell cytotoxicity by preferentially regulating NKp30 expression.Frontiers in immunology · 2024Article
- [Synergistic effect of azacitidine with homoharringtonine by activating the c-MYC/DDIT3/PUMA axis in acute myeloid leukemia].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2023Article
- All-trans retinoic acid induces leukemia resistance to NK cell cytotoxicity by down-regulating B7-H6 expression via c-Myc signaling.Cancer communications (London, England) · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundThe interaction between activating receptor NKp30 and its major tumor ligand B7-H6 is important for NK cell-mediated tumor rejection. However, the regulation of B7-H6 by tumor therapeutics remains largely unknown. In this study, we investigated the regulation of B7-H6 by all-trans retinoic acid (atRA), a terminal differentiation inducer of tumor cells that is extensively used for clinical leukemia therapy.
methodsWe investigated the role of NKp30:B7-H6 axis in NK cell-mediated tumor lysis against leukemia cells and the influence of atRA treatment on the cytotoxicity of NK cells using NK cell lines (NK92 and NKG) and leukemia cell lines (U-937 and THP-1). We evaluated the effect of atRA treatment on the expression of B7-H6 using real-time PCR, flow cytometry and western blotting. We used CRISPR/Cas9 to knockdown B7-H6 expression and siRNA to knockdown c-Myc in U-937 cells to evaluate the role of B7-H6 and c-Myc in atRA-induced tumor resistance against NK cells.
resultsNK cell-mediated U-937 cell lysis was mainly dependent on NKp30/B7-H6 interaction. Blockade of B7-H6 by monoclonal antibody significantly impaired NK cytotoxicity. atRA treatment induced U-937 resistance to NK cell cytotoxicity by reducing B7-H6 expression, and showed no effect on NK cytotoxicity against B7-H6 knockdown U-937 cells. Epigenetic modifications, such as DNA methylation and histone deacetylase (HDAC), were not responsible for atRA-mediated B7-H6 down-regulation as inhibitors of these pathways could not restore B7-H6 mRNA expression. On the other hand, atRA treatment reduced c-Myc expression, which in turn inhibited the transcription of B7-H6 on leukemia cells.
conclusionatRA treatment promotes tumor cell resistance against NK cell-mediated lysis by down-regulating B7-H6 expression via the c-Myc signaling pathway, suggesting that more attention needs to be paid to the immunological adverse effects in the clinical use of atRA treatment.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.