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Methionine consumption by cancer cells drives a progressive upregulation of PD-1 expression in CD4 T cells.

التفاصيل البيبلوغرافية
العنوان: Methionine consumption by cancer cells drives a progressive upregulation of PD-1 expression in CD4 T cells.
المؤلفون: Pandit M; College of Pharmacy, Yeungnam University, Gyeongsan-si, Gyeongsangbukdo, 38541, Republic of Korea., Kil YS; College of Pharmacy, Yeungnam University, Gyeongsan-si, Gyeongsangbukdo, 38541, Republic of Korea., Ahn JH; Department of Pharmacy, Kangwon National University, Chuncheon, 24341, Republic of Korea., Pokhrel RH; College of Pharmacy, Yeungnam University, Gyeongsan-si, Gyeongsangbukdo, 38541, Republic of Korea., Gu Y; College of Pharmacy, Yeungnam University, Gyeongsan-si, Gyeongsangbukdo, 38541, Republic of Korea., Mishra S; College of Pharmacy, Yeungnam University, Gyeongsan-si, Gyeongsangbukdo, 38541, Republic of Korea., Han Y; Department of Pharmacy, Kangwon National University, Chuncheon, 24341, Republic of Korea., Ouh YT; Department of Obstetrics and Gynecology, School of medicine, Kangwon National University, Chuncheon, 24289, Republic of Korea., Kang B; Department of Pediatrics, School of Medicine, Kyungpook National University, 68-Gukchaebosang-ro, Jung-gu, Daegu, 41944, Republic of Korea., Jeong MS; Chuncheon Center, Korea Basic Science Institute (KBSI), Chuncheon, 24341, Republic of Korea.; Department of Biochemistry, Kangwon National University, Chuncheon, 24341, Republic of Korea., Kim JO; College of Pharmacy, Yeungnam University, Gyeongsan-si, Gyeongsangbukdo, 38541, Republic of Korea., Nam JW; College of Pharmacy, Yeungnam University, Gyeongsan-si, Gyeongsangbukdo, 38541, Republic of Korea., Ko HJ; Department of Pharmacy, Kangwon National University, Chuncheon, 24341, Republic of Korea. hjko@kangwon.ac.kr., Chang JH; College of Pharmacy, Yeungnam University, Gyeongsan-si, Gyeongsangbukdo, 38541, Republic of Korea. jchang@yu.ac.kr.
المصدر: Nature communications [Nat Commun] 2023 May 05; Vol. 14 (1), pp. 2593. Date of Electronic Publication: 2023 May 05.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: CD4-Positive T-Lymphocytes* , Neoplasms*/metabolism , Programmed Cell Death 1 Receptor*/metabolism, Animals ; Female ; Mice ; AMP-Activated Protein Kinases/metabolism ; CD8-Positive T-Lymphocytes ; Methionine/metabolism ; Mice, Knockout ; Racemethionine/metabolism ; Up-Regulation
مستخلص: Programmed cell death protein 1 (PD-1), expressed on tumor-infiltrating T cells, is a T cell exhaustion marker. The mechanisms underlying PD-1 upregulation in CD4 T cells remain unknown. Here we develop nutrient-deprived media and a conditional knockout female mouse model to study the mechanism underlying PD-1 upregulation. Reduced methionine increases PD-1 expression on CD4 T cells. The genetic ablation of SLC43A2 in cancer cells restores methionine metabolism in CD4 T cells, increasing the intracellular levels of S-adenosylmethionine and yielding H3K79me2. Reduced H3K79me2 due to methionine deprivation downregulates AMPK, upregulates PD-1 expression and impairs antitumor immunity in CD4 T cells. Methionine supplementation restores H3K79 methylation and AMPK expression, lowering PD-1 levels. AMPK-deficient CD4 T cells exhibit increased endoplasmic reticulum stress and Xbp1s transcript levels. Our results demonstrate that AMPK is a methionine-dependent regulator of the epigenetic control of PD-1 expression in CD4 T cells, a metabolic checkpoint for CD4 T cell exhaustion.
(© 2023. The Author(s).)
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المشرفين على المادة: EC 2.7.11.31 (AMP-Activated Protein Kinases)
AE28F7PNPL (Methionine)
0 (Programmed Cell Death 1 Receptor)
73JWT2K6T3 (Racemethionine)
0 (Pdcd1 protein, mouse)
تواريخ الأحداث: Date Created: 20230505 Date Completed: 20230522 Latest Revision: 20230522
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC10162977
DOI: 10.1038/s41467-023-38316-9
PMID: 37147330
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-023-38316-9