TABLE 2.
TIME compositions | M6A regulators | Molecular mechanisms | Functions | Reference | |
---|---|---|---|---|---|
Immune cells | DC | METTL3, HNRNPC | Regulating CD40 and CD80 expression | DC migration and function | 27, 102 |
YTHDF1, YTHDF2 | Regulating lysosomal protease expression | CCR7‐mediated DC migration and DC‐based immunec responses | 103 | ||
Macrophage | FTO | Regulating STAT1 and PPAR‐γ mRNA degradation | M1 and M2 macrophages polarization | 105 | |
Naïve T cell | METTL3 | Regulating SOCS family mRNA degradation | naïve T cell proliferation and differentiation | 106 | |
Treg | METTL3 | Regulating SOCS family mRNA degradation | Tregs stability and suppressive function | 107 | |
ALKBH5 | Regulating MCT4 expression | Tregs infiltration | 26 | ||
MDSC | METTL3 | MDSCs infiltration | 108 | ||
ALKBH5 | Regulating MCT4 expression | MDSCs infiltration | 26 | ||
Immune checkpoints | PD‐L1 | FTO | Regulating IFN‐γ pathway | PD‐L1 expression | 110 |
LIRB4 | FTO | Regulating mRNA degradation | LIRB4 expression | 88 | |
ULPB2, MICB | IGF2BP3 | ULPB2 and MICB expression and migration | 111 | ||
CD40, CD80 | METTL3, HNRNPC | CD40 and CD80 expression | 27, 102 | ||
Cytokines | IL6, IL12, and TNF‐α | METTL3 | Regulating NF‐κB signaling | Production of IL6, IL12, and TNF‐α | 27 |
IFN‐γ, CXCL9, and CXCL10 | METTL3, METTL14 | Regulating IFN‐γ‐STAT1‐IRF1 signal pathway | Production of IFN‐γ, CXCL9, and CXCL10 | 113 | |
TGF‐β1 | METTL3 | Regulating TGF‐β1 mRNAs degradation and translation elongation | Production and activation of TGF‐β1 | 115 |
m6A, N 6‐methyladenosine; TIME, tumor immune microenvironment; DC, dendritic cell; CCR7, C‐C motif chemokine receptor 7; STAT1, signal transducer and activator of transcription 1; PPAR, peroxisome proliferators‐activated receptor; SOCS, suppressor of cytokine signaling; Treg, regulatory T cells; MCT4, monocarboxylate transporter 4; MDSC, myeloid‐derived suppressor cell; IFN‐γ, interferon gamma; LIRB4, leukocyte immunoglobulin like receptor B4; LIRB4, leukocyte immunoglobulin like receptor B4; MICB, MHC class I polypeptide‐related sequence B; IL‐6, interleukin 6; IL‐12, interleukin 12; TNF‐α, tumor necrosis factor alpha; NK‐κB, nuclear factor kappa B; CXCL9, C‐X‐C motif chemokine ligand 9; CXCL10, C‐X‐C motif chemokine ligand 10; TFG‐β1, transforming growth factor beta 1.