Targeting m 6 A reader YTHDF1 augments antitumour immunity and boosts anti-PD-1 efficacy in colorectal cancer

Objective The role of N 6 -methyladenosine (m 6 A) in tumour immune microenvironment (TIME) remains understudied. Here, we elucidate function and mechanism of YTH N 6 -methyladenosine RNA binding protein 1 (YTHDF1) in colorectal cancer (CRC) TIME. Design Clinical significance of YTHDF1 was assessed in tissue microarrays (N=408) and TCGA (N=526) cohorts. YTHDF1 function was determined in syngeneic tumours, intestine-specific Ythdf1 knockin mice, and humanised mice. Single-cell RNA-seq (scRNA-seq) was employed to profile TIME. Methylated RNA immunoprecipitation sequencing (MeRIP-seq), RNA sequencing (RNA-seq) and ribosome sequencing (Ribo-seq) were used to identify YTHDF1 direct targets. Vesicle-like…

• NN
  National Natural Science Foundation of China

  Award: 81972576
• RG
  Research Grants Council, University Grants Committee

  Award: C4039-19GF, 14110819, 14111621