The Role of m6A Methylation in Tumor Immunity and Immune-Associated Disorder
Abstract
:1. Introduction
2. M6A Methylation-Related Proteins: From Writing to Interpreting
3. M6A Modification in Immune Cells
4. Aberrant m6A Modifications of Immune System Regulation in Human Cancer
4.1. Digestive System
4.1.1. Esophageal Cancer
4.1.2. Gastric Cancer
4.1.3. Liver Cancer
4.1.4. Pancreatic Cancer
4.1.5. Colorectal Cancer (CRC)
4.1.6. Gallbladder Cancer
4.2. Respiratory System
4.2.1. Lung Adenocarcinoma
4.2.2. Nasopharyngeal Carcinoma
4.3. Endocrine System
4.3.1. Thyroid Cancer
4.3.2. Pituitary Adenomas
4.4. Nervous System
4.5. Urinary System
4.5.1. Prostate Cancer
4.5.2. Renal Cell Carcinoma
4.5.3. Bladder Cancer
4.6. Reproductive System
4.6.1. Breast Cancer
4.6.2. Cervical Cancer
4.6.3. Endometrial Cancer
4.6.4. Ovarian Cancer
4.7. Musculoskeletal System
4.7.1. Melanoma
4.7.2. Osteosarcoma
4.8. Acute Myeloid Leukaemia
5. m6A Modification-Association with Immune Regulation and Implications on Autoimmune and Immune-Related Diseases
5.1. Rheumatoid Arthritis, RA
5.2. Systemic Lupus Erythematous, SLE
5.3. Inflammatory Bowel Disease, IBE
5.4. Primary Sjogren Syndrome, pSS
5.5. Ankylosing Spondylitis, AS
5.6. RNA Methylation and Other Autoimmune Diseases
5.7. M6A and Acquired Immunodeficiency Syndrome, AIDS
6. Conclusions and Prospects
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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System | Cancer Type | m6A Regulator | Immune Cell Type | Target Genes | Mechanism | Immunity Expression | Methods of Treatment | Refs. |
---|---|---|---|---|---|---|---|---|
Digestive system | Esophageal squamous cell carcinoma (ESCC) | HNRNPC RBM15 IGF2BP3 METTL16 KIAA1429 | macrophages, neutrophils | negative | [50] | |||
YTHDF2 METL14 KIAA1429 | negative | Immune-checkpointinhibition, PD-L1 | [51] | |||||
YTHDC1 YTHDC2 YTHDC3 ZC3H13 | macrophages | HNRNPA2B1——p53 mutation | positive | [52] | ||||
HNRNPA2B1 | T cell | positive | [52] | |||||
HNRNPC | B cell | positive | Immune-checkpointinhibition, PD-L1 | [52] | ||||
Gastric cancer (GC) | KIAA1429 (recruiting METTL3, METTL14, and WTAP) | DC | C-type lectin receptors, NOD-like receptors, T-cell receptors, toll-like receptors,NF-κB signaling pathways | negative | Immune-checkpointinhibition,PD1/L1 | [53,54] | ||
YTHDF1 | recruitment of DCs, CD4+ and CD8+ T cells, adaptive T-cell | FNGR1 and JAK1/2-STAT1 pathway | negative | [55,56] | ||||
ALKBH5 | naïve B cells, neutrophils, plasma cells, and follicular helper T cells | SLC7A2, CGB3 | positive | [57] | ||||
YTHDF3 | PI3K/AKT pathway | positive | Immune-checkpointinhibition, PD-L1,CXCL1 | [58,59] | ||||
Liver cancer | ALKBH5 | myeloid-derived suppressor-like cells | negative | [60] | ||||
PD-L1+macrophage | MAP3K8 | JNK and ERK pathways | positive | Immune-checkpointinhibition,PD-L1 | [61] | |||
YTHDF2 | T (Treg) cells | NF-κB signaling | negative | [62,63] | ||||
METTL5 | B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils and DCs | ribosomal and oxidative phosphorylation, mismatch repair, spliceosome and other signaling pathways | positive | PD1 (PDCD1),CTLA4 | [64,65,66] | |||
Pancreatic cancer | METTL3 | lncRNA MALAT1 | positive | Immune-checkpointinhibition,PD-L1 | [67,68] | |||
METTL16 | B and CD8+ T cell | positive | Immune-checkpointinhibition | [69] | ||||
Colorectal cancer | YTHDF1 | CD8+Tcell, T cells and NK cells | IFN-γ-related gene | negative | Immune-checkpointinhibition,PD-1 | [70] | ||
granulocytic myeloid-derived suppressor cells (G-MDSCs), neutrophils | YTHDF1-p65-CXCL1/CXCR2 axis | positive | [71] | |||||
METTL14 | dysfunctional T cell | negative | ||||||
METTL3 METTL14 | CD8+ T cells | Stat1 | IFN-γ-Stat1-Irf1 signaling pathway | negative | [72] | |||
ALKBH5 | CD8+ T cells | NF-κB-CCL5 | positive | [73] | ||||
IGF2BP3 | NK CD56dim cells, T helper cells, eosinophils, DC, and macrophage neutrophils | positive | Immune-checkpointinhibition,PD-1, CTLA-4 | [74,75] | ||||
Gallbladder cancer | YTHDF2 | DAPK3 | negative | Chemotherapy, Gemcitabine | [76] | |||
Respiratory system | lung adenocarcinoma | LRPPRC | DC, CD8+ cytotoxic T cells, macrophage | negative | Immune-checkpointinhibition,PD-1 | [77] | ||
METTL3 | CD8 T cells | activation of chemokine signaling pathways, T cell receptor signaling pathways, and B cell receptor signaling pathway | negative | Immune-checkpointinhibition,PD-1 (Nivoumab) | [78] | |||
IGF2BP2 CBLL1 HNRNPA2B1 | CD4 memory activated T cells, resting NK cells, M0 macrophages, M1 macrophages, and resting mast cells | positive | Immune-checkpointinhibition,LAG3 | [79,80] | ||||
YTHDF2 YTHDF3 FTO | negative | Immune-checkpointinhibition, LAG3 | [80] | |||||
Nasopharyngeal Carcinoma | LRPPRC | Th2 cell | negative | Immune-checkpointinhibition,PD-L1 | [81] | |||
ALKBH5 | NK cells, T cells (CD8+ T and CD4+ T), DCs, M1 macrophages | RIG-I | ALKBH5/RIG-I/IFNα | negative | [82] | |||
Endocrine System | Thyroid cancer | METTL3 | CD70 expression and M2 macrophages and Tregs infiltration | negative | Targeted therapy,cusatuzumab | [83] | ||
Pituitary adenomas | YTHDF2 | M2 macrophages | positive | Immune-checkpointinhibition,PD-L1 | [84] | |||
Nervous System | Glioblastoma | FTO ZC3H13 YTHDC1 | TCM cell | positive | [85] | |||
FTO ZC3H13 | macrophages | negative | [85] | |||||
ALKBH5 | CD3, CD4, CD8 T cells | negative | Immune-checkpointinhibition,PD-L1 | [86] | ||||
METTL4 WTAP VIRMA | CD8 + T cells, macrophage cells, and myeloid dendritic cells | TFRC | positive | Immune-checkpointinhibition,PD-L1(cd274),CTLA4 | [87] | |||
WTAP | macrophages | HSPA7 | YAP1-LOX | positive | Immune-checkpointinhibition,PD-1 | [88] | ||
Urinary System | Prostate cancer | METTL14 ZC3H13 | Th1 cells, Th17 cells, stromal fraction and TGF-beta response | positive | Immune-checkpointinhibition,PD-1 | [39,89] | ||
HNRNPC | Treg cells | positive | Immune-checkpointinhibition,CTLA-4 | [90] | ||||
effector CD8 T cell | negative | [90] | ||||||
Kidney renal clear cell carcinoma | METTL14 | CD4+ T cells, CD8+ T cells, neutrophils, natural killer (NK) cells, myeloid dendritic cells, macrophages, and B cells | NF-κB pathway | positive | Immune-checkpointinhibition, CD274(PD-L1),HAVCR2,PDCD1LG2(PD-L2),SIGLEC15,TIGIT | [91,92,93] | ||
METTL14 RBM15B VIRMA ZC3H13 FTO YTHDF2 YTHDC1 HNRNPC1 | CD56 bright NK cells, mast cells, NK cells, pDC | CDH13 | positive | Immune-checkpointinhibition,PDCD1,CD274,PDCD1LG2,CTLA4,LAG3 | [94,95,96] | |||
METTL5 | NK T cell, naïve CD8+T cell, effector memory CD8+ T cell, naïve CD4+ T cell, central memory CD4+ T cell, T helper 1 (Th1) CD4+ T cell, plasma cytoid dendritic cell, myeloid dendritic cell, mast cell, macrophage M2, macrophage M1, macrophage, eosinophil, class-switched memory B cell, plasma B cell, naïve B cell, memory B cell and B cell | negative | [97] | |||||
METTL14 ALKBH5 YTHDC1 RBM15B LRPPRC IGF2BP2 IGF2BP3 | NK cells, neutrophils, endothelial cell | ALDOB | positive or negative correlation is unknown | [98] | ||||
Bladder cancer | FTO IGF2BP3 | M2 macrophage | PGM1, ENO1 | positive | [99] | |||
YTHDC1 | M2 macrophage | PGM1, ENO1 | negative | [99] | ||||
Reproductive System | Cervical cancer | METTL16 YTHDF1 ZC3H13 | negative | Immune-checkpointinhibition,PD-L1 | [100] | |||
IGF2BP3 | Treg cells | GLS, GLUD1 | positive | [101,102] | ||||
METTL3 | CD33+MDSCs | positive | [103] | |||||
Endometrial cancer | METTL14 ZC3H13 YTHDC1 | CD4+ Tell | positive | Immune-checkpointinhibition,PD-L1 | [104] | |||
macrophage | negative | [105,106] | ||||||
Ovarian cancer | NK, T central memory cells (Tcm) and T gamma delta cells | CDC42EP3 | positive | [107,108] | ||||
Breast Cancer | YTHDF1 | T cells CD4 memory activated, macrophages M1, NK cells | WNT pathway | positive | Immune-checkpointinhibition | [109] | ||
HNRNPC VIRMA | CD8 T cells | TFAP2A/DDR1 | negative | [110] | ||||
Musculoskeletal System | Melanoma | FTO | Immune-checkpointinhibition,PD-1, CXCR4, SOX10 | [111,112] | ||||
ALKBH5 | Tregs, PMN-MDSCs | negative | [113,114] | |||||
DCs | positive | Immune-checkpointinhibition,PD-1 | [113,114] | |||||
Acute myeloid leukaemia | METTL14 | most immune cells | negative | Immune-checkpointinhibition,CTAL4 (negative) | [115] | |||
ZC3H13 | most immune cells | positive | Immune-checkpointinhibition,CTAL4 (negative) | [115] | ||||
YTHDC2 | positive | Immune-checkpointinhibition,PD-L1 | [115] | |||||
RBM15 | negative | Immune-checkpointinhibition,PD-L1 | [115] |
Autoimmune Disease | m6A Regulator | Immune Cell Type | Immunity Expression | Target Gene | Mechanism | Treatment | Refs. |
---|---|---|---|---|---|---|---|
Rheumatoid arthritis (RA) | METTL3 | Macrophage polarization (M1) | positive | STAT1 | STAT1 methylation | Sarsasapogenin (Sar) | [41] |
IGF2BP3 | Macrophage polarization (M1) | positive | Fibroblast-like synovial cells (FLS) | G2/M transition | Infliximab | [213] | |
METTL3 | Macrophage | negative | NF-κB signaling pathway | [214] | |||
Systemic lupus erythematosus (SLE) | METTL3 | Treg | negative | SOCS | il-2-stat5 signaling pathway | [215,216] | |
METTL3 | B cell | positive | FOXO3 | [217] | |||
METTL3 | CD4+ T cell, Th1 cell, Th17 cell | positive | [218] | ||||
ALKBH5 | T cell | positive | [219,220] | ||||
Inflammatory bowel disease (IBD) | YTHDC1 | Macrophage | positive | Fine-tuned NME nucleoside diphosphokinase 1 (NME1) | Vitolizumab | [221] | |
METTL14 | T cell | positive | Naïve T cells induce inflammation | Coptisine (COP) | [222] | ||
FTO | Th17 | positive | [223] | ||||
Primary Sjögren’s syndrome (pSS) | METTL3 | Dentric cell and T cell | positive | [224] | |||
Mastocyte | positive | FMR1 | [225] | ||||
ankylosing spondylitis (AS) | METTL14 | Mesenchymal stem cells (MSC) migration | The ALKBH5-PRMT6 axis controls the activation of AKT signaling pathway | [226] | |||
YTHDF2, ALKBH5 | Peripheral blood mononuclear cell (PBMC) | negative | [227] | ||||
Autoimmune Hepatitis (AIH) | YTHDF2 | Bone marrow-derived suppressor cells (MDSCs) | positive | [228] | |||
Autoimmune encephalomyelitis (EAE) | ALKBH5 | CD4+ T cell | negative | IFNG, CXCL2 | IL-17 signaling pathway | [229] | |
Allergic respiratory Disease (ARD) | METTL3 | M2 macrophage | negative | PI3K/AKT and JAK/STAT6 signaling pathway | Methylprednisolone, Chelidonine, Nerabine, Ribavirin | [230] | |
HIV | YTHDF3 | CD4+ T cell | negative | Increasing HIV-1 reverse transcription | Protease inhibitors (indinavir, amprenavir, etc.) | [231,232,233] |
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Mu, S.; Zhao, K.; Zhong, S.; Wang, Y. The Role of m6A Methylation in Tumor Immunity and Immune-Associated Disorder. Biomolecules 2024, 14, 1042. https://doi.org/10.3390/biom14081042
Mu S, Zhao K, Zhong S, Wang Y. The Role of m6A Methylation in Tumor Immunity and Immune-Associated Disorder. Biomolecules. 2024; 14(8):1042. https://doi.org/10.3390/biom14081042
Chicago/Turabian StyleMu, Siyu, Kaiyue Zhao, Shanshan Zhong, and Yanli Wang. 2024. "The Role of m6A Methylation in Tumor Immunity and Immune-Associated Disorder" Biomolecules 14, no. 8: 1042. https://doi.org/10.3390/biom14081042