koko体育app

欢迎来到《koko体育app 学报(医学版)》
免疫力力排泄在肺部肿瘤免疫力力中的功能模块研究方案最新进展

杨扬 范典 郑博豪 周圣涛

杨扬, 范典, 郑博豪, 等. 免疫代谢在肿瘤免疫中的功能研究进展[J]. koko体育app 学报(医学版), 2023, 54(3): 497-504. doi: 10.12182/20230560304
引用本文: 杨扬, 范典, 郑博豪, 等. 免疫代谢在肿瘤免疫中的功能研究进展[J]. koko体育app 学报(医学版), 2023, 54(3): 497-504. doi:
YANG Yang, FAN Dian, ZHENG Bo-hao, et al. Latest Findings on the Function of Immune Metabolism in Tumor Immunity[J]. JOURNAL OF SICHUAN UNIVERSITY (MEDICAL SCIENCES), 2023, 54(3): 497-504. doi: 10.12182/20230560304
Citation: YANG Yang, FAN Dian, ZHENG Bo-hao, et al. Latest Findings on the Function of Immune Metabolism in Tumor Immunity[J]. JOURNAL OF SICHUAN UNIVERSITY (MEDICAL SCIENCES), 2023, 54(3): 497-504. doi:

免疫代谢在肿瘤免疫中的功能研究进展

doi: 
基金项目: 国家自然科学基金(No.81822034)资助
详细信息
    作者简介:

    周圣涛,教授,博士生导师,国家优秀青年科学基金获得者,koko体育app 华西第二医院党委委员,妇科副主任,曾获得2019年度中国肿瘤青年科学家奖,国家科技部“干细胞研究与器官修复”重点研发计划青年首席科学家,第八届“中国青少年科技创新奖”,成都市五四青年奖章等荣誉。现为四川省学术和技术带头人,koko体育app “双百人才工程”首批入选者,担任中华医学会妇科肿瘤分会青委副主任委员,中国抗癌协会肿瘤微环境专委会青委副主任委员等。带领团队长期从事肿瘤免疫微环境分子机制及靶向治疗相关研究,近年来以通信作者身份在Cancer Discov(封面文章)、Sci AdvGenome Biol、PNASCancer ResClin Cancer Res等国际期刊发表多篇学术论文,目前担任Genome BioleLifeBMC BiolOncogeneiScience等期刊编委

    通讯作者:

    E-mail:shengtaozhou@dikai.net.cn

Latest Findings on the Function of Immune Metabolism in Tumor Immunity

More Information
  • 摘要: 代谢重编程是癌症的重要特征,以满足其快速增殖的需求。肿瘤中的代谢变化调控免疫细胞多种代谢途径来实现抗肿瘤免疫抑制。近年来对糖、氨基酸和脂质的代谢变化的研究,以及肿瘤细胞和免疫细胞间代谢调控的相互作用的深入探索,靶向代谢的同时联合现有抗肿瘤疗法,通过满足免疫细胞的代谢需求增强免疫治疗的抗肿瘤效应,为靶向肿瘤免疫代谢治疗、增强抗肿瘤免疫反应提供新的思路。关于新的免疫检查点分子、新型细胞免疫疗法的研究也正在进行。本文对近年来肿瘤免疫抑制的免疫代谢机制及其在免疫治疗中的功能相关研究进展进行综述,并对未来免疫代谢调控的发展进行展望。
  • [1] LI X, WENES M, ROMERO P, et al. Navigating metabolic pathways to enhance antitumour immunity and immunotherapy. Nat Rev Clin Oncol,2019,16(7): 425–441. doi:
    [2] CASCONE T, MCKENZIE J A, MBOFUNG R M, et al. Increased tumor glycolysis characterizes immune resistance to adoptive T cell therapy. Cell Metab,2018,27(5): 977–987. doi:
    [3] ANCEY P B, CONTAT C, MEYLAN E. Glucose transporters in cancer--from tumor cells to the tumor microenvironment. FEBS J,2018,285(16): 2926–2943. doi:
    [4] CORBET C, FERON O. Tumour acidosis: from the passenger to the driver's seat. Nat Rev Cancer,2017,17(10): 577–593. doi:
    [5] LIU X, HOFT D F, PENG G. Senescent T cells within suppressive tumor microenvironments: emerging target for tumor immunotherapy. J Clin Invest,2020,130(3): 1073–1083. doi:
    [6] ANGELIN A, GIL-De-GÓMEZ L, DAHIYA S, et al. Foxp3 reprograms T cell metabolism to function in low-glucose, high-lactate environments. Cell Metab,2017,25(6): 1282–1293.e7. doi:
    [7] LIU X, MO W, YE J, et al. Regulatory T cells trigger effector T cell DNA damage and senescence caused by metabolic competition. Nat Commun,2018,9(1): 249. doi:
    [8] CHANG C H, QIU J, O'SULLIVAN D, et al. Metabolic competition in the tumor microenvironment is a driver of cancer progression. Cell,2015,162(6): 1229–1241. doi:
    [9] LI W, TANIKAWA T, KRYCZEK I, et al. Aerobic glycolysis controls myeloid-derived suppressor cells and tumor immunity via a specific CEBPB isoform in triple-negative breast cancer. Cell Metab,2018,28(1): 87–103.e6. doi:
    [10] HUSAIN Z, HUANG Y, SETH P, et al. Tumor-derived lactate modifies antitumor immune response: effect on myeloid-derived suppressor cells and NK cells. J Immunol,2013,191(3): 1486–1495. doi:
    [11] BOHN T, RAPP S, LUTHER N, et al. Tumor immunoevasion via acidosis-dependent induction of regulatory tumor-associated macrophages. Nat Immunol,2018,19(12): 1319–1329. doi:
    [12] ZHANG W, WANG G, XU Z G, et al. Lactate is a natural suppressor of RLR signaling by targeting MAVS. Cell,2019,178(1): 176–189.e15. doi:
    [13] SUN S, LI H, CHEN J, et al. Lactic acid: no longer an inert and end-product of glycolysis. Physiology (Bethesda),2017,32(6): 453–463. doi:
    [14] PAJAK B, SIWIAK E, SOŁTYKA M, et al. 2-deoxy-d-glucose and its analogs: from diagnostic to therapeutic agents. Int J Mol Sci,2019,21(1): 234. doi:
    [15] CHRISTOFK H R, VANDER HEIDEN M G, HARRIS M H, et al. The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature,2008,452(7184): 230–233. doi:
    [16] HOU P P, LUO L J, CHEN H Z, et al. Ectosomal PKM2 promotes HCC by inducing macrophage differentiation and remodeling the tumor microenvironment. Mol Cell,2020,78(6): 1192–1206.e10. doi:
    [17] ZHOU Y, HUANG Z, SU J, et al. Benserazide is a novel inhibitor targeting PKM2 for melanoma treatment. Int J Cancer,2020,147(1): 139–151. doi:
    [18] HUANG R, JING X, HUANG X, et al. Bifunctional naphthoquinone aromatic amide-oxime derivatives exert combined immunotherapeutic and antitumor effects through simultaneous targeting of indoleamine-2, 3-dioxygenase and signal transducer and activator of transcription 3. J Med Chem,2020,63(4): 1544–1563. doi:
    [19] RIVERA-ÁVALOS E, De LOERA D, ARAUJO-HUITRADO J G, et al. Synthesis of amino acid-naphthoquinones and in vitro studies on cervical and breast cell lines. Molecules,2019,24(23): 4285. doi:
    [20] HSU M C, HUNG W C. Pyruvate kinase M2 fuels multiple aspects of cancer cells: from cellular metabolism, transcriptional regulation to extracellular signaling. Mol Cancer,2018,17(1): 35. doi:
    [21] CURTIS N J, MOONEY L, HOPCROFT L, et al. Pre-clinical pharmacology of AZD3965, a selective inhibitor of MCT1: DLBCL, NHL and Burkitt's lymphoma anti-tumor activity. Oncotarget,2017,8(41): 69219–69236. doi:
    [22] NABE S, YAMADA T, SUZUKI J, et al. Reinforce the antitumor activity of CD8(+) T cells via glutamine restriction. Cancer Sci,2018,109(12): 3737–3750. doi:
    [23] JOHNSON M O, WOLF M M, MADDEN M Z, et al. Distinct regulation of Th17 and Th1 cell differentiation by glutaminase-dependent metabolism. Cell,2018,175(7): 1780–1795.e19. doi:
    [24] LIU P S, WANG H, LI X, et al. α-ketoglutarate orchestrates macrophage activation through metabolic and epigenetic reprogramming. Nat Immunol,2017,18(9): 985–994. doi:
    [25] ALTMAN B J, STINE Z E, DANG C V. From Krebs to clinic: glutamine metabolism to cancer therapy. Nat Rev Cancer,2016,16(10): 619–634. doi:
    [26] GREGORY M A, NEMKOV T, PARK H J, et al. Targeting glutamine metabolism and redox state for leukemia therapy. Clin Cancer Res,2019,25(13): 4079–4090. doi:
    [27] JACQUE N, RONCHETTI A M, LARRUE C, et al. Targeting glutaminolysis has antileukemic activity in acute myeloid leukemia and synergizes with BCL-2 inhibition. Blood,2015,126(11): 1346–1356. doi:
    [28] LUENGO A, GUI D Y, VANDER HEIDEN M G. Targeting metabolism for cancer therapy. Cell Chem Biol,2017,24(9): 1161–1180. doi:
    [29] PAVLOVA N N, HUI S, GHERGUROVICH J M, et al. As extracellular glutamine levels decline, asparagine becomes an essential amino acid. Cell Metab,2018,27(2): 428–438.e5. doi:
    [30] COOLS J. Improvements in the survival of children and adolescents with acute lymphoblastic leukemia. Haematologica,2012,97(5): 635. doi:
    [31] Van TRIMPONT M, SCHALK A M, De VISSER Y, et al. In vivo stabilization of a less toxic asparaginase variant leads to a durable antitumor response in acute leukemia. Haematologica,2023,108(2): 409–419. doi:
    [32] GROHMANN U, MONDANELLI G, BELLADONNA M L, et al. Amino-acid sensing and degrading pathways in immune regulation. Cytokine Growth Factor Rev,2017,35: 37–45. doi:
    [33] HE X, LIN H, YUAN L, et al. Combination therapy with l-arginine and α-PD-L1 antibody boosts immune response against osteosarcoma in immunocompetent mice. Cancer Biol Ther,2017,18(2): 94–100. doi:
    [34] GEIGER R, RIECKMANN J C, WOLF T, et al. L-arginine modulates T cell metabolism and enhances survival and anti-tumor activity. Cell,2016,167(3): 829–842.e13. doi:
    [35] AABOE JØRGENSEN M, UGEL S, LINDER HÜBBE M, et al. Arginase 1-based immune modulatory vaccines induce anticancer immunity and synergize with anti-PD-1 checkpoint blockade. Cancer Immunol Res,2021,9(11): 1316–1326. doi:
    [36] WERNER A, KOSCHKE M, LEUCHTNER N, et al. Reconstitution of T cell proliferation under arginine limitation: activated human T cells take up citrulline via l-type amino acid transporter 1 and use it to regenerate arginine after induction of argininosuccinate synthase expression. Front Immunol,2017,8: 864. doi:
    [37] MUSSAI F, WHEAT R, SARROU E, et al. Targeting the arginine metabolic brake enhances immunotherapy for leukaemia. Int J Cancer,2019,145(8): 2201–2208. doi:
    [38] TARASENKO T N, GOMEZ-RODRIGUEZ J, MCGUIRE P J. Impaired T cell function in argininosuccinate synthetase deficiency. J Leukoc Biol,2015,97(2): 273–278. doi:
    [39] FULTANG L, BOOTH S, YOGEV O, et al. Metabolic engineering against the arginine microenvironment enhances CAR-T cell proliferation and therapeutic activity. Blood,2020,136(10): 1155–1160. doi:
    [40] PLATTEN M, NOLLEN E A A, RÖHRIG U F, et al. Tryptophan metabolism as a common therapeutic target in cancer, neurodegeneration and beyond. Nat Rev Drug Discov,2019,18(5): 379–401. doi:
    [41] MUNN D H, MELLOR A L. IDO in the tumor microenvironment: inflammation, counter-regulation, and tolerance. Trends Immunol,2016,37(3): 193–207. doi:
    [42] MINHAS P S, LIU L, MOON P K, et al. Macrophage de novo NAD(+) synthesis specifies immune function in aging and inflammation. Nat Immunol,2019,20(1): 50–63. doi:
    [43] MULLARD A. IDO takes a blow. Nat Rev Drug Discov,2018,17(5): 307. doi:
    [44] BOCHET L, LEHUÉDÉ C, DAUVILLIER S, et al. Adipocyte-derived fibroblasts promote tumor progression and contribute to the desmoplastic reaction in breast cancer. Cancer Res,2013,73(18): 5657–5668. doi:
    [45] GEERAERTS X, BOLLI E, FENDT S M, et al. Macrophage metabolism as therapeutic rarget for cancer, atherosclerosis, and obesity. Front Immunol,2017,8: 289. doi:
    [46] CHOWDHURY P S, CHAMOTO K, KUMAR A, et al. PPAR-induced fatty acid oxidation in T cells increases the number of tumor-reactive CD8(+) T cells and facilitates anti-PD-1 therapy. Cancer Immunol Res,2018,6(11): 1375–1387. doi:
    [47] LIN R, ZHANG H, YUAN Y, et al. Fatty acid oxidation controls CD8(+) tissue-resident memory T-cell survival in gastric adenocarcinoma. Cancer Immunol Res,2020,8(4): 479–492. doi:
    [48] YANG W, BAI Y, XIONG Y, et al. Potentiating the antitumour response of CD8(+) T cells by modulating cholesterol metabolism. Nature,2016,531(7596): 651–655. doi:
    [49] QIN W H, YANG Z S, LI M, et al. High serum levels of cholesterol increase antitumor functions of nature killer cells and reduce growth of liver tumors in mice. Gastroenterology,2020,158(6): 1713–1727. doi:
    [50] SAG D, CEKIC C, WU R, et al. The cholesterol transporter ABCG1 links cholesterol homeostasis and tumour immunity. Nat Commun,2015,6: 6354. doi:
    [51] MA X, BI E, LU Y, et al. Cholesterol Induces CD8. Cell Metab,2019,30(1): 143–156.e5. doi:
    [52] KANEDA M M, CAPPELLO P, NGUYEN A V, et al. Macrophage PI3Kγ drives pancreatic ductal adenocarcinoma progression. Cancer Discov,2016,6(8): 870–885. doi:
    [53] PILON-THOMAS S, KODUMUDI K N, El-KENAWI A E, et al. Neutralization of tumor acidity improves antitumor responses to immunotherapy. Cancer Res,2016,76(6): 1381–1390. doi:
    [54] KUCHUK O, TUCCITTO A, CITTERIO D, et al. PH regulators to target the tumor immune microenvironment in human hepatocellular carcinoma. Oncoimmunology,2018,7(7): e1445452. doi:
    [55] PALMIERI E M, MENGA A, MARTÍN-PÉREZ R, et al. Pharmacologic or genetic targeting of glutamine synthetase skews macrophages toward an M1-like phenotype and inhibits tumor metastasis. Cell Rep,2017,20(7): 1654–1666. doi:
    [56] WU L, ZHANG X, ZHENG L, et al. RIPK3 orchestrates fatty acid metabolism in tumor-associated macrophages and hepatocarcinogenesis. Cancer Immunol Res,2020,8(5): 710–721. doi:
    [57] NETEA M G, DOMÍNGUEZ-ANDRÉS J, BARREIRO L B, et al. Defining trained immunity and its role in health and disease. Nat Rev Immunol,2020,20(6): 375–388. doi:
    [58] ARTS R J, NOVAKOVIC B, TER HORST R, et al. Glutaminolysis and fumarate accumulation integrate immunometabolic and epigenetic programs in trained immunity. Cell Metab,2016,24(6): 807–819. doi:
    [59] CHENG S C, QUINTIN J, CRAMER R A, et al. MTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity. Science,2014,345(6204): 1250684. doi:
    [60] ARTS R J W, CARVALHO A, La ROCCA C, et al. Immunometabolic pathways in BCG-induced trained immunity. Cell Rep,2016,17(10): 2562–2571. doi:
    [61] KEATING S T, GROH L, THIEM K, et al. Rewiring of glucose metabolism defines trained immunity induced by oxidized low-density lipoprotein. J Mol Med (Berl),2020,98(6): 819–831. doi:
    [62] Van Der HEIJDEN C, GROH L, KEATING S T, et al. Catecholamines induce trained immunity in monocytes in vitro and In vivo. Circ Res,2020,127(2): 269–283. doi:
    [63] KEATING S T, GROH L, Van Der HEIJDEN C, et al. The Set7 lysine methyltransferase regulates plasticity in oxidative phosphorylation necessary for trained immunity induced by β-glucan. Cell Rep,2020,31(3): 107548. doi:
    [64] BEKKERING S, ARTS R J W, NOVAKOVIC B, et al. Metabolic induction of trained immunity through the mevalonate pathway. Cell,2018,172(1/2): 135–146.e9. doi:
    [65] DOMÍNGUEZ-ANDRÉS J, NOVAKOVIC B, LI Y, et al. The itaconate pathway is a central regulatory node linking innate immune tolerance and trained immunity. Cell Metab,2019,29(1): 211–220.e5. doi:
    [66] SOULARUE E, LEPAGE P, COLOMBEL J F, et al. Enterocolitis due to immune checkpoint inhibitors: a systematic review. Gut,2018,67(11): 2056–2067. doi:
    [67] LAG3-PD-1 combo impresses in melanoma. Cancer Discov,2021,11(7): 1605–1606. doi:
    [68] DIXON K O, TABAKA M, SCHRAMM M A, et al. TIM-3 restrains anti-tumour immunity by regulating inflammasome activation. Nature,2021,595(7865): 101–106. doi:
    [69] La-BECK N M, JEAN G W, HUYNH C, et al. Immune checkpoint inhibitors: new insights and current place in cancer therapy. Pharmacotherapy,2015,35(10): 963–976. doi:
    [70] LIZÉE G, OVERWIJK W W, RADVANYI L, et al. Harnessing the power of the immune system to target cancer. Annu Rev Med,2013,64: 71–90. doi:
    [71] LIM S, LIU H, Da SILVA L M, et al. Immunoregulatory protein B7-H3 reprograms glucose metabolism in cancer cells by ROS-mediated stabilization of HIF1α. Cancer Res,2016,76(8): 2231–2242. doi:
    [72] PATSOUKIS N, BARDHAN K, CHATTERJEE P, et al. PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation. Nat Commun,2015,6: 6692. doi:
    [73] SHARMA P, WAGNER K, WOLCHOK J D, et al. Novel cancer immunotherapy agents with survival benefit: recent successes and next steps. Nat Rev Cancer,2011,11(11): 805–812. doi:
    [74] ZHENG W, O'HEAR C E, ALLI R, et al. PI3K orchestration of the in vivo persistence of chimeric antigen receptor-modified T cells. Leukemia,2018,32(5): 1157–1167. doi:
    [75] KAWALEKAR O U, O'CONNOR R S, FRAIETTA J A, et al. Distinct signaling of coreceptors regulates specific metabolism pathways and impacts memory development in CAR T cells. Immunity,2016,44(2): 380–390. doi:
    [76] KLICHINSKY M, RUELLA M, SHESTOVA O, et al. Human chimeric antigen receptor macrophages for cancer immunotherapy. Nat Biotechnol,2020,38(8): 947–953. doi:
  • 加载中
计量
  • 文章访问数:  933
  • HTML全文浏览量:  40
  • PDF下载量:  49
  • 被引次数: 0
出版历程
  • 收稿日期:  2023-05-16
  • 修回日期:  2024-04-26
  • 网络出版日期:  2024-05-20
  • 刊出日期:  2024-05-20

目录

    /

    返回文章
    返回
    var _hmt = _hmt || []; (function() { var hm = document.createElement("script"); hm.src = "https://hm.baidu.com/hm.js?90c4d9819bca8c9bf01e7898dd269864"; var s = document.getElementsByTagName("script")[0]; s.parentNode.insertBefore(hm, s); })(); !function(p){"use strict";!function(t){var s=window,e=document,i=p,c="".concat("https:"===e.location.protocol?"https://":"http://","sdk.51.la/js-sdk-pro.min.js"),n=e.createElement("script"),r=e.getElementsByTagName("script")[0];n.type="text/javascript",n.setAttribute("charset","UTF-8"),n.async=!0,n.src=c,n.id="LA_COLLECT",i.d=n;var o=function(){s.LA.ids.push(i)};s.LA?s.LA.ids&&o():(s.LA=p,s.LA.ids=[],o()),r.parentNode.insertBefore(n,r)}()}({id:"K9y7iMpaU8NS42Fm",ck:"K9y7iMpaU8NS42Fm"}); koko体育-koko体育app koko体育-koko体育网页版koko体育app koko体育-全站app下载(官网) m6米乐app|下载 m6米乐app|主頁欢迎您!!