Table 2 Targeting m6A regulator improves the response to ICI immunotherapy
From: The m6A revolution: transforming tumor immunity and enhancing immunotherapy outcomes
M6A regulator | Malignancy | ICB | drugs | Tumor model | Effects/observations | Refs. |
|---|---|---|---|---|---|---|
METTL3 | CRC | Anti-PD1 | METTL3-single guide RNA/STM2457 | MC38/CT26 allografts | Potentiates the Effect of AntiPD1 Therapy | [101] |
METTL3 | TNBC | Anti-PD1 | STM2457 | AT3 TNBC model | Improved survival for the combination of STM2457 with anti-PD1 therapy | [154] |
METTL3 | NAFLD-HCC | Anti-PD1 | METTL3 knockdown/VNP-si METTL3/STM2457 | Hepa1-6/RIL-175 tumors | Inhibiting METTL3 plus PD-1 blockade improves response to immunotherapy | [139] |
METTL3 | Â | Anti-PD1 | METTL3 knockout | B16 tumour | METTL3 depletion in myeloid cells impairs PD-1 blockade therapeutic efficacy | [64] |
FTO | Â | Anti-PD-L1 | DAC51 | B16-OVA/MC38 tumors | Slower growth of B16-OVA and MC38 tumors, and their overall survival was significantly prolonged | [132] |
FTO | Melanoma | Anti-PD-1 | FTO knockdown | B10F10 | FTO inhibition can reduce resistance to anti-PD-1 therapy | [155] |
FTO | HCC | Anti-PD-1 | CS2 | Orthotopic liver injection mouse model; spontaneous HCC tumours | Sensitised HCC to anti-PD-1 therapy | [142] |
ALKBH5 | CRC | Anti-PD1 | VNP-siALKBH5 | MC38 tumor | Enhances the efficacy of anti-PD1 therapy | [141] |
ALKBH5 | NSCLC | Anti-PD-L1 | ALKBH5 knockdown | LLC allografts | Lung cancer cells with high ALKBH5 expression are more sensitive to anti-PD-L1 therapy | [103] |
YTHDF1 | Â | Anti-PD1 | YTHDF1 knockdown | CT26/MC38 tumours | The combination therapy prolonged OS of mice | [149] |
YTHDF1 | Â | Anti-PD-L1/anti-CTLA-4 | YTHDF1 knockdown | B16/F10 tumours | Tumor-intrinsic YTHDF1 deficiency enhances responses to ICI therapy | [122] |
YTHDF1 | CRC | Anti-PD-1 | VNP-siYTHDF1 | MC38/CT26 syngeneic tumours | Augments anti-PD1 therapy in CRC | [104] |
YTHDF1 | NASH-HCC | Anti-PD1 | LNP-si YTHDF1 | RIL-175 tumor | Synergistically decreased tumor burden | [99] |
YTHDF2 | Â | Anti-PD-L1 | DC-Y13-27 | MC38/B16 tumor | The triple therapy of DC-Y13-27, IR, and anti-PD-L1 gave rise to the most robust antitumor effects | [67] |
YTHDF2 | Â | Anti-PD-L1/anti-PD-1 | DF-A7 | MC38 tumor | Improves antitumor efficacy of PD-1/PD-L1 blockade therapy | [105] |
YTHDF2 | Liver tumor | Anti-PD1 | YTHDF2 knockout | MC38 liver metastatic tumor | The synergistic therapeutic effects of chemotherapy and immunotherapy on liver cancer were dependent on hepatic YTHDF2 expression | [106] |