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In primary gastrointestinal malignancies, such as colorectal cancer (CRC), robust experimental evidence indicates that microbiota-derived ammonia accumulates directly within the local TME, where it actively drives T cell exhaustion and enhances tumor progression ( 2.2 Molecular components: transport proteins, sensors, and effectors The operation of the ammonia signaling network relies on a series of key molecular components responsible for the transmembrane transport of ammonia, the sensing of intracellular concentrations, and the transmission of downstream signals