RNA m6A-Ythdf1 in dendritic cells triggers anti-tumor immunity (MeRIP-Seq, RIP-Seq and Ribo-Seq in Flt3L-DCs)

Emerging evidence emphasizes the important role of tumor neoantigen in generating the spontaneous antitumor immune response and predicting the clinical response to immunotherapies. Despite the presence of numerous neoantigens, complete tumor elimination rarely occurs in majority of patients due to failures in mounting a sufficient and lasting antitumor immunity. Here we show that the durable neoanitgen-specific immunity is regulated by a m6A-binding protein, Ythdf1. In contrast to wild-type mice, Ythdf1-deficient (Ythdf1-/-) mice generate more antigen-specific CD8+ T cell response for persistent tumor control. Loss of Ythdf1 in dendritic cell (DC) results in an enhanced cross-presentation of tumor antigen and cross-priming of CD8+ T cell in vivo. To confirm our observations, we performed Ribo-Seq to analyze the translational efficiency of genes in DCs and performed m6A-seq to locate the m6A sites. Flt3L-DCs obtained from WT and YTHDF1 KO mice were used to generate MeRIP-Seq, RIP-Seq and Ribo-Seq libraries. Two replicates for each conditions.