Han et al. 2019 (PRJNA473808)

General Details

Title RNA m6A-Ythdf1 in dendritic cells triggers anti-tumor immunity (ribo-seq and m6a-seq in GMDCs)
Organism
Number of Samples 12
Release Date 2018/05/30 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP149359
ENA SRP149359
GEO GSE115105
BioProject PRJNA473808

Publication

Title
Authors Han D, Liu J, Chen C, Dong L, Liu Y, Chang R, Huang X, Liu Y, Wang J, Dougherty U, Bissonnette MB, Shen B, Weichselbaum RR, Xu MM, He C
Journal Nature
Publication Date 2019 Feb
Abstract There is growing evidence that tumour neoantigens have important roles in generating spontaneous antitumour immune responses and predicting clinical responses to immunotherapies 1,2 . Despite the presence of numerous neoantigens in patients, complete tumour elimination is rare, owing to failures in mounting a sufficient and lasting antitumour immune response 3,4 . Here we show that durable neoantigen-specific immunity is regulated by mRNA N 6 -methyadenosine (m 6 A) methylation through the m 6 A-binding protein YTHDF1 5 . In contrast to wild-type mice, Ythdf1-deficient mice show an elevated antigen-specific CD8 + T cell antitumour response. Loss of YTHDF1 in classical dendritic cells enhanced the cross-presentation of tumour antigens and the cross-priming of CD8 + T cells in vivo. Mechanistically, transcripts encoding lysosomal proteases are marked by m 6 A and recognized by YTHDF1. Binding of YTHDF1 to these transcripts increases the translation of lysosomal cathepsins in dendritic cells, and inhibition of cathepsins markedly enhances cross-presentation of wild-type dendritic cells. Furthermore, the therapeutic efficacy of PD-L1 checkpoint blockade is enhanced in Ythdf1 -/- mice, implicating YTHDF1 as a potential therapeutic target in anticancer immunotherapy.
PMC PMC6522227
PMID 30728504
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR7235643 PRJNA473808 Mus musculus NA_BMDC Ribo-Seq 0.0
SRR7235644 PRJNA473808 Mus musculus NA_BMDC Ribo-Seq 0.0
SRR7235645 PRJNA473808 Mus musculus NA_BMDC Ribo-Seq 0.0
SRR7235646 PRJNA473808 Mus musculus NA_BMDC Ribo-Seq 0.0
SRR7235647 PRJNA473808 Mus musculus NA_BMDC Ribo-Seq 0.0
SRR7235648 PRJNA473808 Mus musculus NA_BMDC Ribo-Seq 0.0
SRR7235649 PRJNA473808 Mus musculus NA_BMDC Ribo-Seq 0.0
SRR7235650 PRJNA473808 Mus musculus NA_BMDC Ribo-Seq 0.0
SRR7235651 PRJNA473808 Mus musculus NA_BMDC Ribo-Seq 0.0
SRR7235652 PRJNA473808 Mus musculus NA_BMDC Ribo-Seq 0.0
SRR7235653 PRJNA473808 Mus musculus NA_BMDC Ribo-Seq 0.0
SRR7235654 PRJNA473808 Mus musculus NA_BMDC Ribo-Seq 0.0
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)

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