Academic Journal
Metabolic-epigenetic crosstalk in innate immune cell plasticity within the tumor microenvironment.
| Τίτλος: | Metabolic-epigenetic crosstalk in innate immune cell plasticity within the tumor microenvironment. |
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| Συγγραφείς: | Noh J; Department of Biological Sciences and Biotechnology, Chungbuk National University, Cheongju, Korea., Lee J; Department of Biological Sciences and Biotechnology, Chungbuk National University, Cheongju, Korea., You C; Department of Biological Sciences and Biotechnology, Chungbuk National University, Cheongju, Korea., Kang K; Department of Biological Sciences and Biotechnology, Chungbuk National University, Cheongju, Korea. kangk@cbnu.ac.kr. |
| Πηγή: | Experimental & molecular medicine [Exp Mol Med] 2026 Aug; Vol. 58 (8), pp. 2491-2506. Date of Electronic Publication: 2026 Aug 06. |
| Τύπος έκδοσης: | Journal Article; Review |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Nature Publishing Group Country of Publication: United States NLM ID: 9607880 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2092-6413 (Electronic) Linking ISSN: 12263613 NLM ISO Abbreviation: Exp Mol Med Subsets: MEDLINE |
| Imprint Name(s): | Publication: Jan. 2013- : New York : Nature Publishing Group Original Publication: Seoul : Korean Society of Medical Biochemistry and Molecular Biology, 1996- |
| Ιατρικοί όροι (MeSH): | Tumor Microenvironment*/immunology , Tumor Microenvironment*/genetics , Neoplasms*/metabolism , Neoplasms*/immunology , Neoplasms*/pathology , Neoplasms*/genetics , Neoplasms*/etiology , Cell Plasticity*/immunology , Cell Plasticity*/genetics , Immunity, Innate* , Epigenesis, Genetic*, Humans ; Animals ; Metabolic Reprogramming ; Trained Immunity |
| Περίληψη: | The tumor microenvironment exerts profound metabolic and epigenetic pressures that shape the plasticity of innate immune cells, influencing their capacity to promote or suppress tumor progression. Emerging evidence highlights the intricate interplay between metabolic reprogramming and epigenetic modifications in macrophages, neutrophils, and other innate immune populations within the tumor microenvironment. Tumor-derived metabolites, hypoxia, and nutrient availability dynamically regulate chromatin accessibility, histone modifications, and DNA methylation patterns, thereby driving context-dependent immune phenotypes. Notably, metabolic rewiring can imprint long-lasting epigenetic changes, a phenomenon known as innate immune memory, which alters subsequent immune responses. Here, we discuss how key metabolic pathways, including glycolysis, fatty acid oxidation, and amino acid metabolism, govern innate immune cell fate and function via epigenetic mechanisms. We also highlight recent advances in epigenomic profiling that have unveiled distinct chromatin landscapes associated with innate immune dysfunction across cancer types. Finally, we explore emerging therapeutic strategies that target the metabolic-epigenetic axis to restore innate immune surveillance and enhance immunotherapy efficacy. A deeper understanding of this metabolic-epigenetic crosstalk could reveal novel avenues for modulating innate immunity in cancer therapy. (© 2026. The Author(s).) |
| Competing Interests: | Competing interests: The authors declare no competing interests. |
| References: | Science. 2016 Apr 22;352(6284):aaf1098. (PMID: 27102489) Blood. 2007 May 1;109(9):3812-9. (PMID: 17255361) Nature. 2019 May;569(7754):73-78. (PMID: 30996346) Oncogenesis. 2016 Jan 25;5:e190. (PMID: 26807645) J Clin Invest. 2021 Feb 15;131(4):. (PMID: 33320840) J Clin Invest. 2014 Dec;124(12):5466-80. (PMID: 25384214) Nature. 2007 Jun 21;447(7147):972-8. (PMID: 17538624) Science. 2010 Aug 13;329(5993):849-53. (PMID: 20705860) Blood. 2010 Jun 10;115(23):4742-9. (PMID: 20351312) Mol Cell. 2020 Jan 16;77(2):213-227.e5. (PMID: 31735641) Cancer Commun (Lond). 2018 Apr 25;38(1):12. (PMID: 29764521) J Immunother Cancer. 2021 Feb;9(2):. (PMID: 33593829) Cell Rep. 2024 Jun 25;43(6):114308. (PMID: 38829740) Front Immunol. 2023 Dec 05;14:1269896. (PMID: 38116009) Biomed Pharmacother. 2022 Dec;156:113923. (PMID: 36411616) JCI Insight. 2024 Nov 22;9(22):. (PMID: 39388288) Nat Commun. 2019 Jul 25;10(1):3320. (PMID: 31346169) Signal Transduct Target Ther. 2022 Sep 1;7(1):305. (PMID: 36050306) Nature. 2021 Mar;591(7849):306-311. (PMID: 33627871) Antioxid Redox Signal. 2007 Aug;9(8):1221-35. (PMID: 17536958) iScience. 2024 Nov 15;27(12):111359. (PMID: 39660050) Mol Oncol. 2019 Apr;13(4):873-893. (PMID: 30628173) Clin Cancer Res. 2017 Sep 1;23(17):5187-5201. (PMID: 28698201) Annu Rev Immunol. 2014;32:659-702. (PMID: 24655300) Exp Mol Med. 2013 Oct 04;45:e45. (PMID: 24091747) Nat Commun. 2017 Sep 11;8(1):517. (PMID: 28894087) Immunity. 2015 Mar 17;42(3):419-30. (PMID: 25786174) Nat Med. 2007 Jul;13(7):828-35. (PMID: 17603493) J Cancer Res Clin Oncol. 2017 Aug;143(8):1371-1380. (PMID: 28321548) J Clin Invest. 2023 Apr 3;133(7):. (PMID: 36821379) Sci Transl Med. 2025 Apr 9;17(793):eadr4458. (PMID: 40203081) Blood. 2006 Mar 1;107(5):2013-21. (PMID: 16278308) Cell Host Microbe. 2020 Aug 12;28(2):322-334.e5. (PMID: 32544459) Immunity. 2005 May;22(5):633-42. (PMID: 15894280) Nat Metab. 2023 Aug;5(8):1408-1422. (PMID: 37563468) Blood. 2012 Aug 16;120(7):1422-31. (PMID: 22786879) Nat Rev Cancer. 2017 Oct;17(10):577-593. (PMID: 28912578) Cancer Cell. 2024 Mar 11;42(3):474-486.e12. (PMID: 38402610) Nature. 2013 Apr 11;496(7444):238-42. (PMID: 23535595) Oncogene. 2010 Sep 30;29(39):5346-58. (PMID: 20661219) Trends Pharmacol Sci. 2024 Apr;45(4):335-349. (PMID: 38494408) Mol Cell. 2020 Jun 18;78(6):1019-1033. (PMID: 32559423) Nature. 2014 Sep 25;513(7519):559-63. (PMID: 25043024) Sci Adv. 2022 Jan 21;8(3):eabi6696. (PMID: 35044827) Trends Cancer. 2021 Aug;7(8):700-713. (PMID: 34023325) Trends Biochem Sci. 2016 Mar;41(3):211-218. (PMID: 26778478) Cancer Discov. 2021 Apr;11(4):933-959. (PMID: 33811125) Nat Med. 2011 Oct 30;17(11):1498-503. (PMID: 22037646) Nat Med. 2010 Aug;16(8):880-6. (PMID: 20622859) Cell Metab. 2021 Oct 5;33(10):2040-2058.e10. (PMID: 34559989) Mol Cancer. 2025 Mar 05;24(1):66. (PMID: 40038722) Nat Rev Drug Discov. 2020 Nov;19(11):776-800. (PMID: 32929243) Cell Rep. 2024 Feb 27;43(2):113688. (PMID: 38245869) J Immunol. 2010 Feb 1;184(3):1200-9. (PMID: 20026743) Nat Immunol. 2015 Apr;16(4):343-53. (PMID: 25789684) Proc Natl Acad Sci U S A. 2015 Dec 29;112(52):15988-93. (PMID: 26668377) J Immunol. 2015 Jun 15;194(12):6082-9. (PMID: 25964487) Cell. 2016 Nov 17;167(5):1354-1368.e14. (PMID: 27863248) J Immunother Cancer. 2023 Jun;11(6):. (PMID: 37344101) Mol Biomed. 2023 Jun 5;4(1):17. (PMID: 37273004) Science. 2014 Sep 26;345(6204):1251086. (PMID: 25258085) EBioMedicine. 2019 Sep;47:235-246. (PMID: 31462392) Cell Metab. 2022 Nov 1;34(11):1675-1699. (PMID: 36261043) Immunology. 2022 Dec;167(4):451-470. (PMID: 36043705) Immunity. 2024 May 14;57(5):1105-1123.e8. (PMID: 38703775) Cancer Res. 2014 Jul 15;74(14):3652-8. (PMID: 24986517) Nat Rev Immunol. 2021 Aug;21(8):485-498. (PMID: 33526920) J Immunol. 2013 Apr 1;190(7):3783-97. (PMID: 23440412) J Clin Invest. 2020 Jul 1;130(7):3865-3884. (PMID: 32324593) Cell Death Differ. 2024 Dec;31(12):1582-1594. (PMID: 39438765) J Immunol. 2015 Dec 1;195(11):5237-50. (PMID: 26491198) Clin Cancer Res. 2017 Aug 1;23(15):4004-4009. (PMID: 28404599) Nat Immunol. 2024 Dec;25(12):2186-2199. (PMID: 39587347) Elife. 2019 Apr 16;8:. (PMID: 30990168) Signal Transduct Target Ther. 2024 Mar 25;9(1):68. (PMID: 38523155) Immunity. 2015 Mar 17;42(3):393-4. (PMID: 25786167) Nat Rev Immunol. 2015 Jan;15(1):18-29. (PMID: 25534620) Cell Metab. 2016 Nov 8;24(5):657-671. (PMID: 27641098) J Allergy Clin Immunol. 2024 Nov;154(5):1079-1084. (PMID: 39278362) Cell Metab. 2016 Dec 13;24(6):807-819. (PMID: 27866838) Cell. 2013 Jan 17;152(1-2):157-71. (PMID: 23332752) J Immunother Cancer. 2021 Jun;9(6):. (PMID: 34145030) Biomark Res. 2024 Sep 3;12(1):96. (PMID: 39227970) Immunity. 2017 Aug 15;47(2):235-250.e4. (PMID: 28813657) Exp Mol Med. 2025 Oct;57(10):2137-2147. (PMID: 41028520) Science. 2009 May 22;324(5930):1029-33. (PMID: 19460998) Curr Opin Biotechnol. 2020 Jun;63:111-117. (PMID: 31954223) J Biol Chem. 2012 Jul 27;287(31):25758-69. (PMID: 22700961) J Clin Invest. 2013 Sep;123(9):3652-8. (PMID: 23999438) Nat Rev Drug Discov. 2025 Oct;24(10):764-784. (PMID: 40571788) Cell Rep. 2022 Apr 5;39(1):110609. (PMID: 35385733) Cancer Immunol Res. 2015 Nov;3(11):1236-47. (PMID: 26025381) Prog Lipid Res. 2020 Nov;80:101055. (PMID: 32791170) Nat Metab. 2022 Mar;4(3):389-403. (PMID: 35347316) Cell Mol Immunol. 2024 May;21(5):530-532. (PMID: 38632383) Signal Transduct Target Ther. 2025 Jun 4;10(1):178. (PMID: 40461514) Nat Immunol. 2013 Aug;14(8):777-84. (PMID: 23867934) Sci Adv. 2021 Nov 12;7(46):eabi8602. (PMID: 34767443) J Clin Invest. 2019 Feb 1;129(2):631-646. (PMID: 30431439) Proc Natl Acad Sci U S A. 2018 Oct 9;115(41):E9600-E9609. (PMID: 30254159) J Exp Med. 2010 Oct 25;207(11):2439-53. (PMID: 20876310) Nat Commun. 2023 Dec 19;14(1):8353. (PMID: 38114474) Cancer Cell. 2013 Jun 10;23(6):739-52. (PMID: 23707781) Cell Rep. 2024 Feb 27;43(2):113746. (PMID: 38329873) Trends Cancer. 2025 Jul;11(7):629-641. (PMID: 40274457) Genes Dev. 2012 Jun 15;26(12):1326-38. (PMID: 22677546) Cancer Res. 2014 Dec 15;74(24):7250-9. (PMID: 25377469) Mol Cell. 2022 May 5;82(9):1660-1677.e10. (PMID: 35320754) Br J Cancer. 2020 Jan;122(1):4-22. (PMID: 31819192) Cell. 2012 Feb 3;148(3):399-408. (PMID: 22304911) Cancer Lett. 2020 Nov 28;493:266-283. (PMID: 32861706) Signal Transduct Target Ther. 2024 Oct 9;9(1):268. (PMID: 39379377) J Exp Clin Cancer Res. 2023 Sep 23;42(1):245. (PMID: 37740232) Front Cell Dev Biol. 2025 Apr 24;13:1584987. (PMID: 40342932) Cell Death Dis. 2024 Feb 15;15(2):145. (PMID: 38360744) Cell Metab. 2015 Feb 3;21(2):347. (PMID: 29510100) Cell Death Dis. 2024 Nov 8;15(11):801. (PMID: 39516467) Int Immunol. 2020 Jun 26;32(7):485-491. (PMID: 32449776) Nat Rev Cancer. 2014 Nov;14(11):754-62. (PMID: 25291291) Nat Rev Immunol. 2020 Jun;20(6):375-388. (PMID: 32132681) Immunity. 2024 Jan 9;57(1):171-187.e14. (PMID: 38198850) Annu Rev Immunol. 2021 Apr 26;39:583-609. (PMID: 33637019) Trends Immunol. 2019 Aug;40(8):699-718. (PMID: 31301952) Science. 2014 Sep 26;345(6204):1250684. (PMID: 25258083) Cancer Discov. 2021 May;11(5):1067-1081. (PMID: 33504580) Cell Metab. 2006 Mar;3(3):187-97. (PMID: 16517406) Oncoimmunology. 2021 Mar 18;10(1):1896643. (PMID: 33796403) Oncogene. 2016 Sep 22;35(38):4957-72. (PMID: 27109103) Immunity. 2021 Jan 12;54(1):32-43. (PMID: 33220235) Nat Cancer. 2023 Oct;4(10):1455-1473. (PMID: 37653141) Cell Mol Life Sci. 2025 Oct 28;82(1):371. (PMID: 41148321) Cell. 2017 May 4;169(4):570-586. (PMID: 28475890) J Clin Invest. 2022 Nov 15;132(22):. (PMID: 36377658) iScience. 2024 Aug 17;27(9):110750. (PMID: 39280627) Cancer Cell. 2023 Mar 13;41(3):421-433. (PMID: 36801000) Cell. 2015 Jun 18;161(7):1527-38. (PMID: 26073941) Nature. 2008 Jul 24;454(7203):436-44. (PMID: 18650914) Nat Rev Cancer. 2004 Jun;4(6):437-47. (PMID: 15170446) Nat Chem Biol. 2016 Nov;12(11):937-943. (PMID: 27618187) Nat Commun. 2021 Jan 19;12(1):440. (PMID: 33469052) Cell. 2016 Dec 1;167(6):1540-1554.e12. (PMID: 27912061) Science. 2001 Nov 9;294(5545):1337-40. (PMID: 11598268) J Immunol. 2002 Mar 1;168(5):2255-63. (PMID: 11859113) Nat Rev Mol Cell Biol. 2022 May;23(5):369-382. (PMID: 35260831) Cancer Res. 2012 Jun 1;72(11):2746-56. (PMID: 22593198) Nat Rev Immunol. 2021 Mar;21(3):151-161. (PMID: 32839570) Cell. 2019 Jul 11;178(2):346-360.e24. (PMID: 31257026) Biomark Res. 2024 Jan 7;12(1):1. (PMID: 38185636) Cell. 2018 Jan 11;172(1-2):176-190.e19. (PMID: 29328912) Immunity. 2017 Aug 15;47(2):284-297.e5. (PMID: 28813659) Nature. 2020 Sep;585(7824):277-282. (PMID: 32879489) Cancer Cell. 2023 Mar 13;41(3):374-403. (PMID: 36917948) Nat Immunol. 2017 Sep;18(9):985-994. (PMID: 28714978) Cancer Cell. 2009 Sep 8;16(3):183-94. (PMID: 19732719) Nat Immunol. 2014 Apr;15(4):323-32. (PMID: 24562310) Nat Rev Immunol. 2021 Dec;21(12):785-797. (PMID: 33927375) Nature. 2017 Mar 16;543(7645):428-432. (PMID: 28273064) Nucleic Acids Res. 2012 Jun;40(11):4794-803. (PMID: 22323521) Nat Commun. 2023 May 5;14(1):2593. (PMID: 37147330) Signal Transduct Target Ther. 2025 Feb 12;10(1):38. (PMID: 39934144) J Exp Med. 2021 Jan 4;218(1):. (PMID: 33601415) Blood. 2024 Jun 13;143(24):2455-2463. (PMID: 38498044) Nat Rev Drug Discov. 2019 Sep;18(9):669-688. (PMID: 31363227) Nat Rev Drug Discov. 2016 Dec;15(12):835-853. (PMID: 27765940) J Immunol. 2000 Jun 15;164(12):6166-73. (PMID: 10843666) Biochim Biophys Acta Mol Basis Dis. 2019 Dec 1;1865(12):165542. (PMID: 31473341) Cell Metab. 2023 Jul 11;35(7):1101-1113. (PMID: 37390822) Proc Natl Acad Sci U S A. 2019 Jan 22;116(4):1361-1369. (PMID: 30545915) Cell. 2025 May 29;188(11):2992-3012.e16. (PMID: 40318634) PLoS Biol. 2018 May 11;16(5):e2004990. (PMID: 29750788) Cell. 2018 Jan 11;172(1-2):147-161.e12. (PMID: 29328910) Cell. 2023 Aug 31;186(18):3882-3902.e24. (PMID: 37597510) Signal Transduct Target Ther. 2023 May 22;8(1):210. (PMID: 37217462) J Cancer. 2020 Apr 6;11(14):4059-4072. (PMID: 32368288) Signal Transduct Target Ther. 2023 Feb 17;8(1):70. (PMID: 36797231) BMC Cell Biol. 2012 Jul 04;13:18. (PMID: 22762146) Immunity. 2019 Dec 17;51(6):997-1011.e7. (PMID: 31851905) Nat Commun. 2024 Feb 26;15(1):1754. (PMID: 38409200) Cell Metab. 2016 Nov 8;24(5):701-715. (PMID: 27773694) Protein Cell. 2021 Aug;12(8):599-620. (PMID: 33000412) J Biomed Sci. 2025 Sep 10;32(1):87. (PMID: 40931345) Nat Commun. 2019 Jan 18;10(1):338. (PMID: 30659183) Oncoimmunology. 2021 Jul 24;10(1):1956143. (PMID: 34367736) Proc Natl Acad Sci U S A. 2017 Mar 14;114(11):2934-2939. (PMID: 28246332) Immunity. 2018 Jan 16;48(1):147-160.e7. (PMID: 29343435) Hum Mol Genet. 2005 Aug 1;14(15):2231-9. (PMID: 15987702) Dev Cell. 2021 May 17;56(10):1363-1393. (PMID: 33945792) Theranostics. 2025 Jan 13;15(6):2159-2184. (PMID: 39990210) J Biol Chem. 2017 Apr 28;292(17):6882-6894. (PMID: 28330868) Nature. 2019 Oct;574(7779):575-580. (PMID: 31645732) Sci Immunol. 2019 Dec 13;4(42):. (PMID: 31836669) Trends Pharmacol Sci. 2017 Aug;38(8):669-686. (PMID: 28602395) Mol Biomed. 2025 Sep 8;6(1):62. (PMID: 40924040) Cancer Res. 2004 Aug 15;64(16):5839-49. (PMID: 15313928) Cancer Res. 2015 Sep 15;75(18):3771-87. (PMID: 26206559) NPJ Precis Oncol. 2024 Feb 10;8(1):31. (PMID: 38341519) JCI Insight. 2019 Sep 19;4(18):. (PMID: 31534051) J Biol Chem. 2011 Mar 18;286(11):9856-64. (PMID: 21245135) Cell Rep. 2019 Jun 25;27(13):3902-3915.e6. (PMID: 31242422) Nature. 2015 Jul 9;523(7559):231-5. (PMID: 25970248) Cell Rep. 2025 Jan 28;44(1):115206. (PMID: 39798090) Signal Transduct Target Ther. 2021 Jan 1;6(1):2. (PMID: 33384409) J Biol Chem. 2001 Mar 23;276(12):9519-25. (PMID: 11120745) Commun Biol. 2024 Jul 20;7(1):887. (PMID: 39033200) Cancer Res. 2018 Aug 1;78(15):4303-4315. (PMID: 29853605) Cancer Lett. 2024 Jun 28;592:216903. (PMID: 38670307) Cell. 2016 Oct 6;167(2):457-470.e13. (PMID: 27667687) MedComm (2020). 2025 Nov 06;6(11):e70461. (PMID: 41211186) Cell Rep. 2022 Mar 8;38(10):110451. (PMID: 35263597) Immunity. 2018 Dec 18;49(6):1148-1161.e7. (PMID: 30552023) Mol Cell. 2019 Sep 19;75(6):1147-1160.e5. (PMID: 31420217) |
| Grant Information: | RS-2024-00340411 National Research Foundation of Korea (NRF) |
| Entry Date(s): | Date Created: 20260807 Date Completed: 20260903 Latest Revision: 20260905 |
| Update Code: | 20260905 |
| PubMed Central ID: | PMC13538618 |
| DOI: | 10.1038/s12276-026-01802-3 |
| PMID: | 42562887 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 2092-6413 |
|---|---|
| DOI: | 10.1038/s12276-026-01802-3 |