{"id":"41df452d-7cb8-52ce-a78c-2382e93fe0e5","stable_key":"41a89233-da9a-5b7b-9c18-e19bbadcfe2d:methionine-restriction-checkpoint-benefit","predicate":"improves_tested","statement":"Methionine restriction or YTHDF1 depletion increased CD8 infiltration and improved tumor control with PD-1 blockade in the tested mouse models.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"3a0ee1ab-8007-5237-a7f9-cb7d970890e6","mechanism_event_label":"One experimental setting favored restricting the tumor methylation pathway.","subject":{"id":"2fa490e6-50cc-5a22-b1ea-af5e128666e4","slug":"experimental-methionine-restriction","display_name":"Experimentally methionine-restricted diet","entity_type_key":"cellular_process"},"object":{"id":"5f37613b-f829-5c97-8cf6-3ac4b7063cdd","slug":"mouse-mr-ythdf1-antitumor-response","display_name":"Antitumor response in the YTHDF1/m6A mouse study","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"3a0ee1ab-8007-5237-a7f9-cb7d970890e6","stable_key":"41a89233-da9a-5b7b-9c18-e19bbadcfe2d:methionine-restriction-checkpoint-benefit-event","event_type":"observed_relationship","label":"One experimental setting favored restricting the tumor methylation pathway.","description":"Methionine restriction or YTHDF1 depletion increased CD8 infiltration and improved tumor control with PD-1 blockade in the tested mouse models.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"2fa490e6-50cc-5a22-b1ea-af5e128666e4","slug":"experimental-methionine-restriction","display_name":"Experimentally methionine-restricted diet","entity_type_key":"cellular_process"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"5f37613b-f829-5c97-8cf6-3ac4b7063cdd","slug":"mouse-mr-ythdf1-antitumor-response","display_name":"Antitumor response in the YTHDF1/m6A mouse study","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"9d39f561-740b-5f67-bba7-8a72ef612a99","slug":"methionine","display_name":"L-Methionine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Murine tumor models; diet and YTHDF1 perturbations.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Other immune-competent models report harm; diet, tumor stage and microbiome differ. No universal direction or human efficacy is established.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Methionine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"methionine","display_name":"L-Methionine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"One experimental setting favored restricting the tumor methylation pathway.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Methionine deficiency facilitates antitumour immunity by altering m6A methylation of immune checkpoint transcripts. · 2023 · https://pubmed.ncbi.nlm.nih.gov/35803704/ · DOI 10.1136/gutjnl-2022-326928","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"d4faa092-4b9b-5d8b-92d2-9f4260991725","evidence_kind":"source_excerpt","locator":"Lines 452-458","start_line":452,"end_line":458,"excerpt":"## methionine-restriction-checkpoint-benefit\nOne experimental setting favored restricting the tumor methylation pathway.\nMethionine restriction or YTHDF1 depletion increased CD8 infiltration and improved tumor control with PD-1 blockade in the tested mouse models.\nModel: Murine tumor models; diet and YTHDF1 perturbations.\nLimitations: Other immune-competent models report harm; diet, tumor stage and microbiome differ. No universal direction or human efficacy is established.\nEvidence access: Primary abstract\nMethionine deficiency facilitates antitumour immunity by altering m6A methylation of immune checkpoint transcripts. · 2023 · https://pubmed.ncbi.nlm.nih.gov/35803704/ · DOI 10.1136/gutjnl-2022-326928","model_system":"Murine tumor models; diet and YTHDF1 perturbations.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"d969b004-ccc2-5bb4-9109-8ac649137ad1","stable_key":"import-41a89233-da9a-5b7b-9c18-e19bbadcfe2d","title":"L-Methionine: transport, methylation, sulfur metabolism and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. 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