Methionine-driven YTHDF1 expression facilitates bladder cancer progression by attenuating RIG-I-modulated immune responses and enhancing the eIF5B-PD-L1 axis DOI Creative Commons
Anze Yu, Liangmin Fu,

Lanyu Jing

et al.

Cell Death and Differentiation, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 13, 2024

Abstract The impact of amino acids on tumor immunotherapy is gradually being uncovered. In this study, we screened various essential and non-essential found that methionine enhances mRNA methylation reduced the activation Type I interferon pathway in bladder cancer. Through RNA sequencing, point mutations, MB49 mouse models, single-cell demonstrated high levels elevate expression m 6 A reader YTHDF1, promoting degradation RIG-I, thereby inhibiting RIG-I/MAVS-mediated IFN-I reducing efficacy immunotherapy. Additionally, immunoprecipitation mass spectrometry revealed YTHDF1 binds to eukaryotic translation initiation factor eIF5B, which acts PD-L1 enhance its promote immune evasion. By intravesical administration oncolytic bacteria VNP20009, effectively depleted locally, significantly prolonging survival enhancing cell infiltration differentiation within tumors. Multiplex immunofluorescence assays cancer patients confirmed our findings. Our research elucidates two mechanisms by inhibits proposes a targeted depletion strategy advances while minimizing nutritional patients.

Language: Английский

Methionine-driven YTHDF1 expression facilitates bladder cancer progression by attenuating RIG-I-modulated immune responses and enhancing the eIF5B-PD-L1 axis DOI Creative Commons
Anze Yu, Liangmin Fu,

Lanyu Jing

et al.

Cell Death and Differentiation, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 13, 2024

Abstract The impact of amino acids on tumor immunotherapy is gradually being uncovered. In this study, we screened various essential and non-essential found that methionine enhances mRNA methylation reduced the activation Type I interferon pathway in bladder cancer. Through RNA sequencing, point mutations, MB49 mouse models, single-cell demonstrated high levels elevate expression m 6 A reader YTHDF1, promoting degradation RIG-I, thereby inhibiting RIG-I/MAVS-mediated IFN-I reducing efficacy immunotherapy. Additionally, immunoprecipitation mass spectrometry revealed YTHDF1 binds to eukaryotic translation initiation factor eIF5B, which acts PD-L1 enhance its promote immune evasion. By intravesical administration oncolytic bacteria VNP20009, effectively depleted locally, significantly prolonging survival enhancing cell infiltration differentiation within tumors. Multiplex immunofluorescence assays cancer patients confirmed our findings. Our research elucidates two mechanisms by inhibits proposes a targeted depletion strategy advances while minimizing nutritional patients.

Language: Английский

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