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Role of m6A modifications in immune evasion and immunotherapy

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Abstract

RNA modification has garnered increasing attention in recent years due to its pivotal role in tumorigenesis and immune surveillance. N6-methyladenosine (m6A) modification is the most prevalent RNA modification, which can affect the expression of RNA by methylating adenylate at the sixth N position to regulate the occurrence and development of tumors. Dysregulation of m6A affects the activation of cancer-promoting pathways, destroys immune cell function, maintains immunosuppressive microenvironment, and promotes tumor cell growth. In this review, we delve into the latest insights into how abnormalities in m6A modification in both tumor and immune cells orchestrate immune evasion through the activation of signaling pathways. Furthermore, we explore how dysregulated m6A modification in tumor cells influences immune cells, thereby regulating tumor immune evasion via interactions within the tumor microenvironment (TME). Lastly, we highlight recent discoveries regarding specific inhibitors of m6A modulators and the encapsulation of m6A-targeting nanomaterials for cancer therapy, discussing their potential applications in immunotherapy.

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Abbreviations

m6A:

N6-methyladenosine

TME:

Tumor microenvironment

m5C:

5-Methylcytosine

m7G:

N7-methylguanosine

m1A:

N1-methyladenosine

ncRNA:

Non-coding RNA

METTL3:

Methyltransferase-like 3

METTL14:

Methyltransferase-like 14

WTAP:

Wilms tumor-associated protein

RBM15:

RNA-binding motif 15

METTL16:

Methyltransferase-like 16

FTO:

Fat mass and obesity-associated protein

ALKBH5:

Alkb homolog 5

ALKBH3:

Alkb homolog 5

YTH:

YTH-domain family protein

IGF2BP:

Insulin growth factor-2 mRNA-binding proteins

HNRNP:

Heterogeneous nuclear ribo nucleo protein

SAM:

S-adenosylmethionine

IFN:

Interferon

TBK1:

TANK-binding kinase 1

IRF3:

Interferon regulatory factor 3

PD-L1:

Programmed death ligand-1

PD-1:

Programmed death-1

JAK:

Janus kinase

STAT:

Signal transducer and activator of transcription

JNK:

C-Jun N-terminal kinase

HBV:

Hepatitis B virus

PTEN:

Phosphatase and tensin homolog

RIG-I:

Retinoic acid-inducible gene-I

IFN-α:

Interferon α

YTHDF3:

YTH-domain-containing family protein-3

PD-L1:

Programmed death-ligand-1

circRNA:

Circular RNA

YTHDC2:

YTH-domain-containing-2

IFN-γ:

Interferon γ

ETV5:

ETS Variant Transcription Factor 5

MAPK:

Mitogen-activated protein kinase

NK cell:

Natural killer cell

IL-15:

Interleukin-15

ERK:

Extracellular regulated protein kinase

mTOR:

Mechanistic target of rapamycin kinase

NF-κB:

Nuclear factor-κB

SOCS:

Suppressor Of Cytokine Signaling

IL-7:

Interleukin 7

Treg:

Regulatory T-cell

IL-2:

Interleukin 7

TAM:

Tumor-associated macrophages

IL-27:

Interleukin 27

IL-35:

Interleukin 35

lncRNA:

Long non-coding RNA

DC cell:

Dendritic cell

TLR4:

Toll like receptor 4

TIM cell:

Tumor-infiltrating myeloid cell

MDSCs cell:

Myeloid-derived suppressor cells

IL-8:

Interleukin 8

TGF-β:

Transforming growth factor β

p65:

Rela, RELA Proto-Oncogene, NF-KB Subunit

CXCL1:

C-X-C Motif Chemokine Ligand 1

EMT:

Epithelial-mesenchymal transformation

IFNGR1:

Interferon γ receptor 1

TNF-α:

Tumor necrosis factor α

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Acknowledgements

The figures are created with Biorender.com.

Funding

This work was supported partially by grants from the National Natural Science Foundation of China (81903138) and the Natural Science Foundation of Hunan Province (2019JJ50778).

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Authors and Affiliations

  1. NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China

    Chunyu Wu, Qianjin Liao, Pan Chen, Can Guo, Zhaoyang Zeng & Wei Xiong

  2. Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China

    Chunyu Wu, Lvyuan Li, Qiling Tang, Zhaoyang Zeng & Wei Xiong

Authors
  1. Chunyu Wu
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  2. Lvyuan Li
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  3. Qiling Tang
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  4. Qianjin Liao
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  5. Pan Chen
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  6. Can Guo
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  7. Zhaoyang Zeng
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  8. Wei Xiong
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Contributions

All authors contributed to the study conception and design. The first draft of the manuscript was written by C.Y.W, L.Y.L, and Q.L.T and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Wei Xiong.

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Wu, C., Li, L., Tang, Q. et al. Role of m6A modifications in immune evasion and immunotherapy. Med Oncol 41, 159 (2024). https://doi.org/10.1007/s12032-024-02402-9

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