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. 2021 Sep 26;11(9):e525. doi: 10.1002/ctm2.525

TABLE 2.

m6A‐mediated TIME remodeling in various aspects

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.