H3K4 trimethylation regulates cancer immunity: a promising therapeutic target in combination with immunotherapy

@article{Xiao2023H3K4TR,
  title={H3K4 trimethylation regulates cancer immunity: a promising therapeutic target in combination with immunotherapy},
  author={Chu Xiao and Tao Fan and Yujia Zheng and He Tian and Ziqin Deng and Jing-Jun Liu and Chunxiang Li and Jie He},
  journal={Journal for Immunotherapy of Cancer},
  year={2023},
  volume={11},
  url={https://api.semanticscholar.org/CorpusID:260705225}
}
The mechanisms by which H3K4me3 and its modifiers regulate antitumor immunity are delineated, the therapeutic potential of the H3 k4 trimethylation-related agents combined with immunotherapies are explored, and novel epigenetic therapies and immunotherapy-based combination regimens are explored.
View on BMJ
jitc.bmj.com
17 Citations
Background Citations
3

17 Citations

The epigenetic hallmarks of immune cells in cancer

The latest molecular and clinical insights into how DNA modifications, histone modification, and epitranscriptome-related regulations shape immune cells of various cancers are reviewed.

Epigenetic Modulations in Triple-Negative Breast Cancer: Therapeutic Implications for Tumor Microenvironment.

Targeting LSD1 in cancer: molecular elucidation and recent advances.

The Wdr5-H3K4me3 Epigenetic Axis Regulates Pancreatic Tumor Immunogenicity and Immune Suppression

It is reported here that WDR5 exhibits a higher expression level in human pancreatic tumor tissues compared with adjacent normal pancreas and that WDR5 not only regulates tumor cell immunogenicity to suppress tumor growth but also activates immune suppressive pathways to promote tumor immune evasion.

Signatures of H3K4me3 modification predict cancer immunotherapy response and identify a new immune checkpoint-SLAMF9

A new H3K4me3-associated biomarker system to predict tumor immunotherapy response is provided and the preclinical rationale for investigating the roles of SLAMF9 in cancer immunity regulation and treatment is suggested.

Transglutaminase 2-mediated histone monoaminylation and its role in cancer

Recent advances in TGM2-mediated histone monoaminylation as well as its role in cancer are summarized and the key research methodologies to better understand this unique epigenetic mark are discussed, thereby shedding light on the therapeutic potential of TGM2 as a druggable target in cancer treatment.

Integrative Analysis of Multi-Omics Data to Identify Deregulated Molecular Pathways and Druggable Targets in Chronic Lymphocytic Leukemia

The value of integrating omics data to uncover deregulated proteins and pathways in cancer and suggest new therapeutic avenues for CLL are demonstrated.

Unveiling the Role of Histone Methyltransferases in Psoriasis Pathogenesis: Insights from Transcriptomic Analysis

Overall, aberrant expression and isoform variability of histone methyltransferases likely contribute to psoriasis pathogenesis by dysregulating proliferation, differentiation, and immune responses.

ZNF131-BACH1 transcriptionally accelerates RAD51-dependent homologous recombination repair and therapy-resistance of non-small-lung cancer cells by preventing their degradation from CUL3

Findings indicate that ZNF131 exhibits heightened expression in NSCLC, driving essential processes such as proliferation, invasion, and stemness by transcriptionally activating RAD51.

Menin inhibitor MI-503 exhibits potent anti-cancer activity in osteosarcoma

The findings demonstrated the potent anti-OS activity of MI-503 in both in vitro and in vivo models, which also indicated that Menin inhibitor may be a prospective therapeutic strategy for human OS.

174 References

Targeting the epigenetic regulation of antitumour immunity

How epigenetic regulators can be modulated with small-molecule drugs to promote antitumour immune responses is highlighted, and the opportunities and challenges for developing cancer treatment regimens that combine epigenetic therapies with immunotherapies are discussed.

Epi-drugs in combination with immunotherapy: a new avenue to improve anticancer efficacy

The current strategies to increase immunotherapy responses, the effects of HDACi and DNMTi on immune modulation, and the advantages of combinatorial therapy over single-drug treatment are described.

Epigenetic modifiers as new immunomodulatory therapies in solid tumours

In an era where immune therapies are becoming a treatment backbone in many tumour types, epigenetic modifiers could play a crucial role in modulating tumours' immunogenicity and sensitivity to immune agents.

Combining epigenetic drugs with other therapies for solid tumours — past lessons and future promise

The mechanisms by which epi-drugs can modulate the sensitivity of cancer cells to other forms of anticancer therapy, including chemotherapy, radiation therapy, hormone therapy, molecularly targeted therapy and immunotherapy are described and clinical trial designs and drug development strategies aimed at optimizing the development of such combinations are outlined.

Epigenetic therapy in immune-oncology

Evidence is presented that epigenetic therapies can induce the expression of endogenous retroviruses and cancer–testis antigens normally silenced by DNA methylation in most somatic cells, leading to an innate immune response in cancer cells, and implications for combination therapy with epigenetic drugs and immunotherapies.

In vivo epigenetic CRISPR screen identifies Asf1a as an immunotherapeutic target in Kras-mutant lung adenocarcinoma.

Mechanistic studies revealed that tumor cell-intrinsic Asf1a deficiency induced immunogenic macrophage differentiation in the tumor microenvironment by upregulating GM-CSF expression and potentiated T cell activation in combination with anti-PD-1.

EZH2 Inhibitor GSK126 Suppresses Antitumor Immunity by Driving Production of Myeloid-Derived Suppressor Cells.

It is reported that suppressing EZH2 activity using GSK126 resulted in increased numbers of myeloid-derived suppressor cells (MDSC) and fewer CD4+ and IFNγ+CD8+ T cells, which are involved in antitumor immunity, and suggested that modulating the tumor immune microenvironment may improve the efficacy of EZh2 inhibitors.

The Interplay Between Epigenetic Regulation and CD8+ T Cell Differentiation/Exhaustion for T Cell Immunotherapy

It is expressed the perspective that regulating the interplay between epigenetic changes and transcriptional programs provides translational implications of current immunotherapy for cancer treatments.

LSD1 Ablation Stimulates Anti-tumor Immunity and Enables Checkpoint Blockade

Epigenetic regulation of immune checkpoints and T cell exhaustion markers in tumor-infiltrating T cells of colorectal cancer patients.

Epigenetic modifications in promoters of immune checkpoint and T-cell exhaustion genes could induce their upregulation, and potentially implicate the use of epigenetic modifiers to enhance antitumor immunity in CRC patients.
...