Ythdf1, also known as YTH N6-methyladenosine RNA binding protein 1, is an m6A reader protein. It binds to m6A-modified mRNA and is involved in regulating mRNA translation, thus playing a crucial role in various biological processes. It participates in pathways related to tumor immune microenvironment regulation, cell growth, DNA damage repair, and neuronal translation [1-4]. Genetic models, such as gene knockout (KO) and conditional knockout (CKO) mouse models, are valuable tools for studying its functions.

In cancer research, Ythdf1 KO in mouse models has shown significant impacts. In colorectal cancer, genetic depletion of Ythdf1 augmented antitumor immunity, reducing myeloid-derived suppressor cells (MDSCs) and increasing cytotoxic T cells. Ythdf1 promoted CRC through an m6A-p65-CXCL1/CXCR2 axis [1]. In NASH-HCC, Ythdf1 knockout synergized with anti-PD-1 treatment to suppress tumor growth, as Ythdf1 induced MDSC accumulation and CD8+ T-cell dysfunction via the EZH2-IL-6 axis [2]. In breast cancer, Ythdf1 knockdown sensitized cells to chemotherapeutic drugs, as it promotes cell growth and DNA damage repair [3]. In tumors, Ythdf1 deficiency can convert cold tumors into hot tumors, improving the efficacy of immune checkpoint inhibitors by inhibiting MHC-I degradation [4].

In conclusion, Ythdf1 is a key regulator in multiple biological processes. Studies using KO/CKO mouse models have revealed its role in promoting tumorigenesis, immune evasion, and chemoresistance in various cancers, suggesting it as a potential therapeutic target for cancer immunotherapy and overcoming chemoresistance.